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The search for life-supporting molecules in outer space is an ever-growing endeavour. Towards this, the computational chemistry supporting the astronomical spectroscopic observations is becoming a valuable tool to unravel the complex chemical network in interstellar medium (ISM). In the present work, quantum-mechanical computations, accounting for anharmonic effects, are performed to obtain the rotational and vibrational line-data for the gas-phase conformers of proteinogenic amino acid Leucine and its isomeric species predicted to be involved in its stereoinversion under the extreme environment of ISM. These species exhibit diverse chemistry including branched skeleton and zwitterionic ammonium ylides. A few of the species have significantly high dipole moment, which can act as tracer for the conformers of Leucine having low dipole moment. Besides this, the species, which are terrestrially less stable, can be of significant importance to the astronomers. Notably, the spectral database generated in this work can assist in the detection of proteinogenic Leucine and its isomeric species in different regions of ISM.

Selenocysteine (Sec), a rare naturally proteinogenic amino acid, is the major form of essential trace element selenium in living organisms. Selenoproteins, with one or several Sec residues, are found in all three domains of life. Many selenoproteins play a role in critical cellular functions such as maintaining cell redox homeostasis. Sec is usually encoded by an in-frame stop codon UGA in the selenoprotein mRNA, and its incorporation in vivo is highly species-dependent and requires the reprogramming of translation. This mechanistic complexity of selenoprotein synthesis poses a big challenge to produce synthetic selenoproteins. To understand the functions of natural as well as engineered selenoproteins, many strategies have recently been developed to overcome the inherent barrier for recombinant selenoprotein production. In this review, we will describe these progresses in selenoprotein production methodology.

The most unique, essential biomaterial in living beings is Calcium and their species are playing versatile roles in many biological functions. The proton containing and non proton forms of binary species of calcium ion with valine are ML+, MLH2+ and ML2H+ predicted at specific ion strength in disparate aprotic-aqua compositions. The stability constants of these species and their few influenced factors are examined. The differences in log β with respected to dielectric property of the aprotic solvent (1/D) and species formation equilibrium also discussed with reference to their percentages of species distribution curves.

Here, we report the growth of bioelectret crystal films of L-leucine on conductive substrates and detail the first quantitative measurements of the direct piezoelectric effect in this proteinogenic amino acid. Through extensive electromechanical characterisation, we demonstrate that L-leucine is a promising candidate material for use in non-toxic, biocompatible and biodegradable energy harvesting and sensing devices. The data presented here is among, if not the, largest set of quasi-static, longitudinal piezoelectric measurements on crystalline films of a proteinogenic amino acid to date. We substantiate these measurements using a combination of density functional theory calculations and optical microscopy. Our data provides a further example of the enormous unexploited potential of amino acids and similar biological materials in flexible energy harvesting applications. Their combination of sizeable piezoelectric strain constants and extremely low elastic and dielectric constants makes them ideal as biocompatible replacements for toxic, expensive inorganic piezoelectric materials.

Totopotensamide A (TPM A, 1) is a polyketide-peptide glycoside featuring a nonproteinogenic amino acid 4-chloro-6-methyl-5,7-dihydroxyphenylglycine (ClMeDPG). The biosynthetic gene cluster (BGC) of totopotensamides (tot) was previously activated by manipulating transcription regulators in marine-derived Streptomyces pactum SCSIO 02999. Herein, we report the heterologous expression of the tot BGC in Streptomyces lividans TK64, and the production improvement of TPM A via in-frame deletion of two negative regulators totR5 and totR3. The formation of ClMeDPG was proposed to require six enzymes, including four enzymes TotC1C2C3C4 for 3,5-dihydroxyphenylglycine (DPG) biosynthesis and two modifying enzymes TotH (halogenase) and TotM (methyltransferase). Heterologous expression of the four-gene cassette totC1C2C3C4 led to production of 3,5-dihydroxyphenylglyoxylate (DPGX). The aminotransferase TotC4 was biochemically characterized to convert DPGX to S-DPG. Inactivation of totH led to a mutant accumulated a deschloro derivative TPM H1, and the ΔtotHi/ΔtotMi double mutant afforded two deschloro-desmethyl products TPMs HM1 and HM2. A hydrolysis experiment demonstrated that the DPG moiety in TPM HM2 was S-DPG, consistent with that of the TotC4 enzymatic product. These results confirmed that TotH and TotM were responsible for ClMeDPG biosynthesis. Bioinformatics analysis indicated that both TotH and TotM might act on thiolation domain-tethered substrates. This study provided evidence for deciphering enzymes leading to ClMeDPG in TPM A, and unambiguously determined its absolute configuration as S.

The structure of the metabolic network is highly conserved, but we know little about its evolutionary origins. Key for explaining the early evolution of metabolism is solving a chicken–egg dilemma, which describes that enzymes are made from the very same molecules they produce. The recent discovery of several nonenzymatic reaction sequences that topologically resemble central metabolism has provided experimental support for a “metabolism first” theory, in which at least part of the extant metabolic network emerged on the basis of nonenzymatic reactions. But how could evolution kick-start on the basis of a metal catalyzed reaction sequence, and how could the structure of nonenzymatic reaction sequences be imprinted on the metabolic network to remain conserved for billions of years? We performed an in vitro screening where we add the simplest components of metabolic enzymes, proteinogenic amino acids, to a nonenzymatic, iron-driven reaction network that resembles glycolysis and the pentose phosphate pathway (PPP). We observe that the presence of the amino acids enhanced several of the nonenzymatic reactions. Particular attention was triggered by a reaction that resembles a rate-limiting step in the oxidative PPP. A prebiotically available, proteinogenic amino acid cysteine accelerated the formation of RNA nucleoside precursor ribose-5-phosphate from 6-phosphogluconate. We report that iron and cysteine interact and have additive effects on the reaction rate so that ribose-5-phosphate forms at high specificity under mild, metabolism typical temperature and environmental conditions. We speculate that accelerating effects of amino acids on rate-limiting nonenzymatic reactions could have facilitated a stepwise enzymatization of nonenzymatic reaction sequences, imprinting their structure on the evolving metabolic network., The evolutionary origins of metabolism are largely unknown. This study shows that the prebiotically available proteinogenic amino acid cysteine can promote the metabolism-like rate-limiting formation of ribose-5-phosphate, suggesting that early metabolic pathways could have emerged thought the stepwise enzymatization of non-enzymatic reaction sequences.

Amino acids (AAs) are important biomolecules responsible for plethora of functions in both prokaryotic and eukaryotic systems. There are 22 naturally occurring amino acids, among which 20 common amino acids appear in the genetic code and known as proteinogenic amino acids, which are the building blocks of proteins. Proteinogenic amino acids exist in two isomeric forms (except glycine) and the biological activity is often attributed to a specific stereoisomer. Most of the amino acids found in protein is predominantly L-AAs. A few D-amino acids can be found in bacterial cell wall, some marine invertebrates and higher organisms including frog, snail, spider, rat, chicken and human. Besides their role in protein synthesis, different proteinogenic amino acid stereoisomers have found to perform important biological roles either by functioning as precursors of a myriad of other bioactive molecules or by indicating several biological phenomena i.e. acting as markers for different physiological conditions. Given the biological importance of L- and D-amino acids (AAs), improved analytical methods for their resolution and accurate quantification remain of keen interest. Chiral analysis of amino acids in complex biological matrices poses numerous analytical challenges that are exacerbated by broad differences in polarity and ionization efficiencies of the proteinogenic amino acid stereoisomers. To date, various analytical methods are reported for chiral amino acid analysis including chromatographic, spectrometric, enzymatic, fluidic, electrophoretic and microbiological techniques. Advances in stationary phase, derivatization chemistry and instrumentation contributed to achieving baseline separation and accurate detection of trace levels of proteinogenic amino acids stereoisomers in different matrices. However, liquid and gas chromatography coupled to mass spectrometry based analytical methods remain the most popular platform in chiral amino acid analysis in terms of feasibility and performance. This review discusses different physicochemical and biological features and functions of proteinogenic amino acid stereoisomers and lists a variety of established chromatography and mass spectrometry based analytical methods for their analysis reported to date.

Human dietary exposure to the environmental neurotoxin β-N-methylamino-L-alanine (BMAA) has been implicated in an increased risk of developing sporadic neurodegenerative diseases like Alzheimer's and amyotrophic lateral sclerosis. Evidence suggests that humans are exposed to BMAA globally, but very little is known about BMAA metabolism in mammalian systems, let alone in humans. The most plausible, evidence-based mechanisms of BMAA toxicity rely on the metabolic stability of the amino acid and that, following ingestion, it enters the circulatory system unmodified. BMAA crosses from the intestinal lumen into the circulatory system, and the small intestine and liver are the first sites for dietary amino acid metabolism. Both tissues have substantial amino acid metabolic needs, which are largely fulfilled by dietary amino acids. Metabolism of BMAA in these tissues has been largely overlooked, yet is important in gauging the true human exposure risk. Here we investigate the potential for BMAA metabolism by the human liver and small intestine, using in vitro cell systems. Data show that BMAA metabolism via common proteinogenic amino acid metabolic pathways is negligible, and that in the presence of other amino acids cellular uptake of BMAA is substantially reduced. These data suggest that the majority of ingested BMAA remains unmodified following passage through the small intestine and liver. This not only supports oral BMAA exposure as a plausible exposure route to toxic doses of BMAA, but also supports previous notions that protein deficient diets or malnutrition may increase an individual's susceptibility to BMAA absorption and subsequent toxicity.

Amide bond formation is one of the most important reactions in both chemistry and biology1–4, but there is currently no chemical method of achieving α-peptide ligation in water that tolerates all of the 20 proteinogenic amino acids at the peptide ligation site. The universal genetic code establishes that the biological role of peptides predates life’s last universal common ancestor and that peptides played an essential part in the origins of life5–9. The essential role of sulfur in the citric acid cycle, non-ribosomal peptide synthesis and polyketide biosynthesis point towards thioester-dependent peptide ligations preceding RNA-dependent protein synthesis during the evolution of life5,9–13. However, a robust mechanism for aminoacyl thioester formation has not been demonstrated13. Here we report a chemoselective, high-yielding α-aminonitrile ligation that exploits only prebiotically plausible molecules—hydrogen sulfide, thioacetate12,14 and ferricyanide12,14–17 or cyanoacetylene8,14—to yield α-peptides in water. The ligation is extremely selective for α-aminonitrile coupling and tolerates all of the 20 proteinogenic amino acid residues. Two essential features enable peptide ligation in water: the reactivity and pKaH of α-aminonitriles makes them compatible with ligation at neutral pH and N-acylation stabilizes the peptide product and activates the peptide precursor to (biomimetic) N-to-C peptide ligation. Our model unites prebiotic aminonitrile synthesis and biological α-peptides, suggesting that short N-acyl peptide nitriles were plausible substrates during early evolution.

—The trace element selenium, which was discovered by Berzelius in 1817, remains poorly investigated and exhibits diverse and surprising functions. We consider it unique for several reasons. First, it is present not only in organic or inorganic compounds but also in the amino acids selenocysteine and selenomethionine, as a key component, and in selenoproteins, which are found in all Domains of life. Second, selenocysteine is the 21st proteinogenic amino acid. Its uniqueness lies not only in the fact that it is encoded by one of the three stop codons of translation but in that its biosynthesis possesses unique features and that this process involves unique cis- and trans-active factors that are necessary for the recognition of this triplet as selenocysteine-encoding to avoid premature translation termination and synthesize full-sized selenoproteins. The maintenance of these cis- and trans-active factors is energy consuming, which suggests the crucial importance of selenoproteins for an organism. In addition, the pathways of amino-acid and selenoprotein biosynthesis have some distinctive features in different Domains of life. Third, the processes and effects of selenium compounds of different origins, in which this micronutrient plays key roles, are strikingly diverse, especially in the regulation of vital functions in mammals. This review uses the most recent data to present a comprehensive view of the properties and functions of selenium and to provide insight into the uniqueness of this micronutrient.

l-4-Chlorokynurenine (l-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder. Recently, this amino acid was naturally found as a residue in the lipopeptide antibiotic taromycin. Herein, we report the unprecedented conversion of l-tryptophan into l-4-Cl-Kyn catalyzed by four enzymes in the taromycin biosynthetic pathway from the marine bacterium Saccharomonospora sp. CNQ-490. We used genetic, biochemical, structural, and analytical techniques to establish l-4-Cl-Kyn biosynthesis, which is initiated by the flavin-dependent tryptophan chlorinase Tar14 and its flavin reductase partner Tar15. This work revealed the first tryptophan 2,3-dioxygenase (Tar13) and kynurenine formamidase (Tar16) enzymes that are selective for chlorinated substrates. The substrate scope of Tar13, Tar14, and Tar16 was examined and revealed intriguing promiscuity, thereby opening doors for the targeted engineering of these enzymes as useful biocatalysts.

Versatile approaches to nanoparticle synthesis offer unprecedented opportunities for the development of optoelectronics, photonics, and biosciences. With the current advancement of hybrid organic–i...

The first product of sulfate assimilation in plants, cysteine, is a proteinogenic amino acid and a source of reduced sulfur for plant metabolism. Cysteine synthesis is the convergence point of the three major pathways of primary metabolism: carbon, nitrate, and sulfate assimilation. Despite the importance of metabolic and genetic coordination of these three pathways for nutrient balance in plants, the molecular mechanisms underlying this coordination, and the sensors and signals, are far from being understood. This is even more apparent in C4 plants, where coordination of these pathways for cysteine synthesis includes the additional challenge of differential spatial localization. Here we review the coordination of sulfate, nitrate, and carbon assimilation, and show how they are altered in C4 plants. We then summarize current knowledge of the mechanisms of coordination of these pathways. Finally, we identify urgent questions to be addressed in order to understand the integration of sulfate assimilation with carbon and nitrogen metabolism particularly in C4 plants. We consider answering these questions to be a prerequisite for successful engineering of C4 photosynthesis into C3 crops to increase their efficiency., This review summarizes current knowledge on the coordination of sulfur, nitrogen, and carbon metabolism and discusses sulfate assimilation in the context of evolution of C4 photosynthesis.

Novel sophisticated derivatizing agents for the efficient enantioselective separation and mass spectrometric detection of d - and l -amino acids have been developed. Two new axially chiral reagents derived from 6,6′-dimethyl-2,2′-biphenyldiamine were synthesized. Their chiral separation and detection abilities were evaluated by derivatizing proteinogenic amino acid standards in reversed-phase liquid chromatography–tandem mass spectrometry (LC–MS/MS). The resulting diastereomers derived from the developed derivatizing agents and amino acids could be completely separated, because of the effective chiral environment constructed by the axially chiral biphenyl moiety. After optimizing the reactive group, (R)-4-nitrophenyl N-[2′-(diethylamino)-6,6′-dimethyl-[1,1′-biphenyl]-2-yl]carbamate hydrochloride ((R)-BiAC) was found to be the best reagent for highly sensitive simultaneous d , l -amino acid analysis. Using (R)-BiAC, the complete chiral separation of all derivatized proteinogenic amino acids was achieved within 11.5 min with Rs greater than 1.9, except for certain allo-isomers. An exceptional feature of this reagent was its control of elution order, i.e., it afforded elution of the diastereomers derived from d -amino acids before their l -amino acid counterparts for all 19 proteinogenic amino acids. Sensitive detection was also achieved by introducing a dialkyl amino group and selectively cleaving it at the binding site between the reagent and amino acid. Attomole (amol) detection limits (signal-to-noise ratio = 3) were obtained for the tested d , l -amino acids, in the range 7.0–127 amol. As an example of application, the method was applied to food sample analysis, and detected several d -amino acids. Consequently, the developed method seems likely to facilitate simultaneous determination of enantiomers, including the tiny amounts of d -amino acids found in nature.

Pyrrolysine (Pyl, O) exists in nature as the 22nd proteinogenic amino acid. Despite being a fundamental building block of proteins, studies of Pyl have been hindered by the difficulty and inefficiency of both its chemical and biological syntheses. Here, we improve Pyl biosynthesis via rational engineering and directed evolution of the entire biosynthetic pathway. To accommodate toxicity of Pyl biosynthetic genes in Escherichia coli, we also develop Alternating Phage Assisted Non-Continuous Evolution (Alt-PANCE) that alternates mutagenic and selective phage growths. The evolved pathway provides 32-fold improved yield of Pyl-containing reporter protein compared to the rationally engineered ancestor. Evolved PylB mutants are present at up to 4.5-fold elevated levels inside cells, and show up to 2.2-fold increased protease resistance. This study demonstrates that Alt-PANCE provides a general approach for evolving proteins exhibiting toxic side effects, and further provides an improved pathway capable of producing substantially greater quantities of Pyl-proteins in E. coli., Pyrrolysine (Pyl) exists in nature as the 22nd proteinogenic amino acid, but studies of Pyl have been hindered by the difficulty and inefficiency of both its chemical and biological syntheses. Here, the authors developed an improved PANCE approach to evolve the pylBCD pathway for increased production of Pyl proteins in E. coli.

Tellurium is a versatile heavy chalcogen with numerous applications in chemical biology, providing valuable probes in mass cytometry, fluorescence imaging and structural biology. L-Tellurienylalanine (TePhe) is an analogue of the proteinogenic amino acid L-phenylalanine (Phe) in which the phenyl side chain has been replaced by a 5-membered tellurophene moiety. High incorporation level of TePhe in expressed proteins at defined sites is expected to facilitate studies in proteomics, protein NMR spectroscopy, and structure elucidation. As a model we chose immunoglobulin-binding Protein G, B1 domain (GB1) to validate TePhe as a suitable structural analogue for Phe. We demonstrate that approximately 1 in 2 of all Phe sites within GB1 can be substituted with TePhe through expression in standard non-Phe-auxotrophic E. coli in Phe-deficient media containing glyphosate, an inhibitor of aromatic amino acid biosynthesis. The TePhe content of the GB1 sample can be further increased to 85 % through HPLC. Using NMR and CD spectroscopy, we confirm that the Phe-to-TePhe substitution has negligible impact on the global structure and stability of GB1.

With outer space being speculated as the source of handedness in molecules of biological importance, there is a great need to explore the gas-phase stereoinversion in molecules under the conditions akin to interstellar medium. In this work, quantum-mechanical computations are performed to trace the pathways for gas-phase stereoinversion in isoleucine, an amino acid with two chiral centres. Contrary to the previous such work on a two-chiral centre proteinogenic amino acid, threonine, the present work could not trace a complete stereoinversion pathway on the potential energy surface of isoleucine. The failure in case of isoleucine is attributed to its branched aliphatic side chain which hindered a complete inversion in isoleucine. However, the diastereomeric conversion pathways explored in this work for isoleucine support the distribution of different stereoisomers reported in the meteoritic composition. Notably, this study also revealed that the chirality of the aldehydic precursors may hold the key to enantio-biasing observed for isoleucine in the meteoritic samples.

Nicotinamide adenine dinucleotide (NAD+) is a life essential molecule involved in versatile biological processes. To date, only two de novo biosynthetic routes to NAD+ are described, both of which start from a proteinogenic amino acid and are tightly controlled. Here, a de novo quinolinic acid pathway starting from chorismate, which provides an alternative route (named as the C3N pathway) to NAD+ biosynthesis, is established. Significantly, the C3N pathway yields extremely high cellular concentrations of NAD(H) in E. coli. Its utility in cofactor engineering is demonstrated by introducing the four‐gene C3N module to cell factories to achieve higher production of 2,5‐dimethylpyrazine and develop an efficient C3N‐based whole‐cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms., An alternative NAD+ de novo biosynthesis pathway (chorismate‐initial, C3N) decouples the NAD+ de novo biosynthesis from proteins biosynthesis. The C3N module serves a powerful tool for increasing cellular NAD(H) concentrations. Its applications in cofactor engineering are demonstrated in the 2,5‐dimethylpyrazine and chiral amines biocatalysis systems. The wide distribution of chorismate implies a general utility of C3N pathway in versatile organisms.

More than 50% of proteinogenic amino acid sidechains can bind metal ions, enabling proteins and peptides to bear these ions as cofactors. Nevertheless, post-translational modifications and incorporation of noncanonical amino acids bestow peptides and proteins myriads of other coordination capabilities, thanks to an enhanced metal binding. Here we summarize selected examples of natural and artificial systems that contain one or more noncanonical amino acids coordinating a metal ion and subsequently achieve a new or enhanced function. We report on a wide array of systems: from disease-related proteins that undergo sulfurylation or phosphorylation through natural metallophores that selectively capture precious essential ions to synthetic selfassembly strategies, biocatalysts, and chelating agents against toxic metals. Regardless of their (bio)synthetic routes, all possess unique metal-binding properties that could not be effectively achieved by systems composed of canonical residues.

Only twode novobiosynthetic routes to nicotinamide adenine dinucleotide (NAD+) have been described, both of which start from a proteinogenic amino acid and are tightly controlled. Here we establish a C3N pathway starting from chorismate inEscherichia colias a third NAD+de novobiosynthesis pathway. Significantly, the C3N pathway yielded extremely high cellular concentrations of NAD(H) inE. coli. Its utility in cofactor engineering was demonstrated by introducing the four-gene C3N module to cell factories to achieve higher production of 2,5-dimethylpyrazine and develop an efficient C3N-based whole-cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms.

We developed a simple and rapid method for analyzing nonproteinogenic amino acids that does not require conventional chromatographic equipment. In this technique, nonproteinogenic amino acids were first converted to a proteinogenic amino acid through in vitro metabolism in a cell extract. The proteinogenic amino acid generated from the nonproteinogenic precursors were then incorporated into a reporter protein using a cell-free protein synthesis system. The titers of the nonproteinogenic amino acids could be readily quantified by measuring the activity of reporter proteins. This method, which combines the enzymatic conversion of target amino acids with translational analysis, makes amino acid analysis more accessible while minimizing the cost and time requirements. We anticipate that the same strategy could be extended to the detection of diverse biochemical molecules with clinical and industrial implications.

Proline is a proteinogenic amino acid with conformational rigidity and is a pre-requisite for primary metabolism. Proline has been extensively reported for its potential role in osmotic adjustment in plant cells. More the stress regulatory properties of proline have been affirmed by a plethora of researchers. Proline metabolism includes its synthesis and degradation. The synthesis takes place by the glutamate and ornithine pathways. Proline anabolism is induced and its catabolism is suppressed during dehydration, but rehydration stimulates the inverse regulation. Under abiotic stress conditions, the plant synthesizes enormous amounts of various compatible solutes or osmoprotectants including proline. Proline has been found to play a regulatory function in the growth and development of plants by acting as a signaling molecule. Proline is also known to protect photosystem II by protecting the thylakoid membranes from oxidative stress. There is little knowledge about the post-translational modification of enzymes of the proline metabolic pathway.

Non-ribosomal peptide biosynthesis produces highly diverse natural products through a complex cascade of enzymatic reactions that together function with high selectivity to produce bioactive peptides. The modification of non-ribosomal peptide synthetase (NRPS)-bound amino acids can introduce significant structural diversity into these peptides and has exciting potential for biosynthetic redesign. However, the control mechanisms ensuring selective modification of specific residues during NRPS biosynthesis have previously been unclear. Here, we have characterised the incorporation of the non-proteinogenic amino acid 3-chloro-β-hydroxytyrosine during glycopeptide antibiotic (GPA) biosynthesis. Our results demonstrate that the modification of this residue by trans-acting enzymes is controlled by the selectivity of the upstream condensation domain responsible for peptide synthesis. A proofreading thioesterase works together with this process to ensure that effective peptide biosynthesis proceeds even when the selectivity of key amino acid activation domains within the NRPS is low. Furthermore, the exchange of condensation domains with altered amino acid specificities allows the modification of such residues within NRPS biosynthesis to be controlled, which will doubtless prove important for reengineering of these assembly lines. Taken together, our results indicate the importance of the complex interplay of NRPS domains and trans-acting enzymes to ensure effective GPA biosynthesis, and in doing so reveals a process that is mechanistically comparable to the hydrolytic proofreading function of tRNA synthetases in ribosomal protein synthesis.

As a semi-essential proteinogenic amino acid and biothiol, cysteine (Cys) is highly important in many basic cellular processes. Several two-photon (TP) fluorescent probes for Cys detection have been developed, but they are still far away from practical application due to the relatively short wavelength (

The chalcogen elements oxygen, sulfur, and selenium are essential constituents of side chain functions of natural amino acids. Conversely, no structural and biological function has been discovered so far for the heavier and more metallic tellurium element. In the methionine series, only the sulfur-containing methionine is a proteinogenic amino acid, while selenomethionine and telluromethionine are natural amino acids that are incorporated into proteins most probably because of the tolerance of the methionyl-tRNA synthetase; so far, methoxinine the oxygen analogue has not been discovered in natural compounds. Similarly, the chalcogen analogues of tryptophan and phenylalanine in which the benzene ring has been replaced by the largely isosteric thiophene, selenophene, and more recently, even tellurophene are fully synthetic mimics that are incorporated with more or less efficiency into proteins via the related tryptophanyl- and phenylalanyl-tRNA synthetases, respectively. In the serine/cysteine series, also selenocysteine is a proteinogenic amino acid that is inserted into proteins by a special translation mechanism, while the tellurocysteine is again most probably incorporated into proteins by the tolerance of the cysteinyl-tRNA synthetase. For research purposes, all of these natural and synthetic chalcogen amino acids have been extensively applied in peptide and protein research to exploit their different physicochemical properties for modulating structural and functional properties in synthetic peptides and rDNA expressed proteins as discussed in the following review.

The separation mechanism of amino acid enantiomers using a chiral crown ether-bonded stationary phase, CROWNPAK CR-I(+), and acetonitrile (ACN)-rich mobile phases (MPs) was studied. The retention factors of proteinogenic l - amino acids (except proline) formed U-shaped plots against the ACN content in the MP with a sharp increase at a high ACN content, while d - amino acids showed much smaller increases or monotonous decreases in retention within the same range. The use of an acidic, highly organic MP with trifluoroacetic acid (TFA) provided a high enantioselectivity with a short separation time from the contribution of the increased binding of the ammonium group of the analytes to the crown ether functionality of the stationary phase and electrostatic repulsion counteracting the hydrophilic partition mechanism. Optimizing the sample diluent and MP alleviated the peak distortion caused by a moving water band that accompanied the hydrophilic interaction liquid chromatography-like elution conditions. The liquid chromatography/time-of-flight mass spectrometry method with the optimized MP — ACN/ethanol/water/TFA = 80/15/5/0.5 (v/v/v/v) — enabled the determination of eighteen pairs of proteinogenic amino acid enantiomers within 10 min. The conditions also provided the following advantages: (i) fast and highly reproducible separations under isocratic conditions, (ii) high sensitivity and low backpressure using the MP with a high organic content, and (iii) highly reliable peak identification by combining two columns (CR-I(+) and CR-I(-)), reversing the elution orders of the enantiomers.

The proteinogenic composition of yeast extract products varies from experience for manufacturing reasons, though also due to the yeast starting product. Therefore, this study is the first to focus solely on the influence of three industrially applicable cell disruption methods (cell mill, ultrasonic sonotrode and autolysis) on the amino acid and protein composition of a yeast extract. A consistent spent yeast (Saccharomyces cerevisiae TUM 68) produced in a standardized industrial pilot top-fermenting process was used as a raw material for the first time. The disruption effectiveness of autolysis (98%) was higher than that of the mechanical methods (80%), as well as the cleavage of amino acids from the cell protein (307, 155 and 115 mg per g yeast extract for autolysis, sonotrode and cell mill). The proteinogenic amino acid release profiles were dependent upon the disruption methods. The greater the released quantity of an amino acid during autolysis, the more the mean value fluctuated in the prepared yeast extract. Protein size fractionation of the extract using electrophoresis showed differences ranging between 1.5 and 95 kDa. All yeast extracts evidenced good nutritional potential according to FAO/WHO standards. The calculated data showed that the manufacturing method has a big impact on the proteinogenic composition of a yeast extract and the spent yeast TUM 68 used in this study can yield a protein-rich yeast extract.

Sulfur-containing molecules participate in many essential biological processes. Of utmost importance is the methylthioether moiety, present in the proteinogenic amino acid methionine and installed in tRNA by radical-S-adenosylmethionine methylthiotransferases. Although the thiol-ene reaction for carbon-sulfur bond formation has found widespread applications in materials or medicinal science, a biocompatible chemo- and regioselective hydrothiolation of unactivated alkenes and alkynes remains elusive. Here, we describe the design of a general chemoselective anti-Markovnikov hydroalkyl/aryl thiolation of alkenes and alkynes-also allowing the biologically important hydromethylthiolation-by triplet-triplet energy transfer activation of disulfides. This fast disulfide-ene reaction shows extraordinary functional group tolerance and biocompatibility. Transient absorption spectroscopy was used to study the sensitization process in detail. The hereby gained mechanistic insights were successfully employed for optimization of the catalytic system. This photosensitized transformation should stimulate bioimaging applications and carbon-sulfur bond-forming late-stage functionalization chemistry, especially in the context of metabolic labelling.

Methionine is a proteinogenic amino acid that can be post-translationally modified. It is now well established that reactive oxygen species can oxidise methionine residues within living cells. For a long time, it has been thought that such a modification represents merely an inevitable damage derived from aerobic metabolism. However, several authors have begun to contemplate a possible role for this methionine modification in cell signalling. During the last years, a number of proteomic studies have been carried out with the purpose of detecting proteins containing oxidised methionines. Although these proteomic works allow to pinpoint those methionines being oxidised, they are also arduous, expensive and time-consuming. For these reasons, computational approaches aimed at predicting methionine oxidation sites in proteins become an appealing alternative. In the current work, we address methionine oxidation prediction by combining computational intelligence methods with feature engineering and feature selection techniques to improve the efficacy of several machine learning models, while reducing the number of input characteristics needed to get high accuracy rates. We compare random forests, support vector machines, neural networks and flexible discriminant analysis models. Random forests give the best AUC ($$0.8124 \pm 0.0334$$) and accuracy rates ($$0.7590 \pm 0.0551$$) by using only a reduced set of 16 characteristics. These results surpass the outcomes of previous works. In addition, we present an end-user script that has been developed to take a protein ID as an input and return a list with the oxidation state of all the methionine residues found in the analysed protein. Finally, to illustrate the applicability of this tool, we have selected the human $$\alpha 1$$-antitrypsin protein as a case study. This protein was selected because it was not present among the set of proteins used to build up the predictive models but the protein has been well characterised experimentally in terms of methionine oxidation. The prediction returned by our script fully matches the empirical evidence. Out of the nine methionine residues found in this protein, our model predicts the oxidation of only two of them, M351 and M358, which have been reported, on the base of mass spectrometry analyses, to be particularly susceptible to oxidation.

Amino acids constitute the key sources of nitrogen for growth of Candida albicans. In order to survive inside the host in different and rapidly changing environments, this fungus must be able to adapt via its expression of genes for amino acid metabolism. We analysed the ARO8, ARO9, YER152C, and BNA3 genes with regards to their role in the nutritional flexibility of C. albicans. CaAro8p is undoubtedly the most versatile enzyme among the aminotransferases investigated. It is involved in the catabolism of histidine, lysine, and aromatic amino acids as well as in l-Lys, Phe and Tyr biosynthesis. CaAro9p participates in the catabolism of aromatic amino acids and lysine at high concentrations of these compounds, with no biosynthetic role. Conversely, the CaYer152Cp catalytic potential for aromatic amino acid catabolism observed in vitro appears to be of little importance in vivo. Neither biosynthetic nor catabolic roles of CaBan3p were observed for any proteinogenic amino acid. Finally, none of the analysed aminotransferases was solely responsible for the catabolism of a single particular amino acid or its biosynthesis.

Novel peroxosolvates of the non-proteinogenic amino acids sarcosine C3H7NO2·H2O2 (1) and phenylserine C9H11NO3·H2O2 (2) were prepared and their structures were determined by X-ray crystallography. All «active» hydrogen atoms (amino, hydroxo, and peroxo) in these adducts are involved in hydrogen bonding. All H2O2 molecules form two donor hydrogen bonds HOOH⋯−O2C–. In contrast to the widely studied structures of natural amino acid peroxosolvates, in structure 2 charge-assisted NH+⋯O2H2 hydrogen bonds were not found. Crystal 2 represents a rare example of peroxide molecules combined in infinite H-bonded chains.

Selenocysteine, the selenium-containing analogue of cysteine, is the twenty-first proteinogenic amino acid. Since its discovery almost fifty years ago, it has been exploited in unnatural systems even more often than in natural systems. Selenocysteine chemistry has attracted the attention of many chemists in the field of chemical biology owing to its high reactivity and resulting potential for various applications such as chemical modification, chemical protein (semi)synthesis, and protein folding, to name a few. In this Minireview, we will focus on the chemistry of selenium and selenocysteine and their utility in protein chemistry.

Fluorine is an element with unusual properties that has found significant utility in the design of synthetic small molecules, ranging from therapeutics to materials. In contrast, only a few fluorinated compounds made by living organisms have been found to date, most of which derive from the fluoroacetate/fluorothreonine biosynthetic pathway first discovered in Streptomyces cattleya. While fluoroacetate has long been known to act as an inhibitor of the tricarboxylic acid cycle, the fate of the amino acid fluorothreonine is still not well understood. Here, we show that fluorothreonine can be misincorporated into protein in place of the proteinogenic amino acid threonine. We have identified two conserved proteins from the organofluorine biosynthetic locus, FthB and FthC, that are involved in managing fluorothreonine toxicity. Using a combination of biochemical, genetic, physiological, and proteomic studies, we show that FthB is a trans-acting transfer RNA (tRNA) editing protein, which hydrolyzes fluorothreonyl-tRNA 670-fold more efficiently than threonyl-RNA, and assign a role to FthC in fluorothreonine transport. While trans-acting tRNA editing proteins have been found to counteract the misacylation of tRNA with commonly occurring near-cognate amino acids, their role has yet to be described in the context of secondary metabolism. In this regard, the recruitment of tRNA editing proteins to biosynthetic clusters may have enabled the evolution of pathways to produce specialized amino acids, thereby increasing the diversity of natural product structure while also attenuating the risk of mistranslation that would ensue.

Pyrrolysine is the 22nd proteinogenic amino acid encoded into proteins in response to amber (TAG) codons in a small number of archaea and bacteria. The incorporation of pyrrolysine is facilitated by a specialized aminoacyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNAPyl). The secondary structure of tRNAPyl contains several unique features not found in canonical tRNAs. Numerous studies have demonstrated that the PylRS/tRNAPyl pair from archaea is orthogonal in E. coli and eukaryotic hosts, which has led to the widespread use of this pair for the genetic incorporation of non-canonical amino acids. In this brief review we examine the work that has been done to elucidate the structure of tRNAPyl, its interaction with PylRS, and survey recent progress on the use of tRNAPyl as a tool for genetic code expansion.

We have combined results from several spectroscopic techniques to investigate the aerobic reactions of Rh2(AcO)4 (AcO– = CH3COO–) with l-cysteine (H2Cys) and its derivatives d-penicillamine (3,3′-dimethylcysteine, H2Pen), with steric hindrance at the thiol group, and N-acetyl-l-cysteine (H2NAC), with its amino group blocked. Previous investigations have shown that antitumor active dirhodium(II) carboxylates may irreversibly inhibit enzymes containing a thiol group at or near their active sites. Also, cysteine, the only thiol-containing proteinogenic amino acid, interacts in vivo with this class of antitumor compounds, but structural information on the products of such reactions is lacking. In the present study, the reactions of Rh2(AcO)4 and H2L were carried out in aqueous solutions at the pH of mixing (acidic) and at physiological pH, using the different mole ratios 1:2, 1:4, and 1:6, which resulted in the same products in increasing yields. Electrospray ionization mass spectrometry (ESI-MS) indicates fo...

In this paper is proposed a new theory concerning the formation of the first proteinogenic amino acids and their corresponding polypeptides starting of three syntones: methylene, nitrene and carbon monoxide. First, at low temperature in nitrogen, these three syntones form aziridinone, an asimetric compound in special conditions. Next, by a series of radical chain, izomerization, cyclization, elimination and polymerization reactions, apparently without a well defined transition states are formed a series of precursor syntones. Finally, these more structured syntones at the contract with the components of primary atmosphere, especially with water, ammonia, hydrogen sulphide, even with carbon dioxide and methane offer the first proteinogenic amino acids and their first corresponding polypeptides. As a very important aspect, the aziridinone cycle furnish the backbone of proteinogenic amino acids. The formation of each proteinogenic amino acid moiety also as its participation to construction of polypeptide structures were estimated by two parameters: (1) the complex structural factor,Feand (2) the participation coefficient,Cprespectively. Dominantly, the quantitative results given in this paper were acquired by structural, thermodynamical and reactivity studies using DGauss with the B88-LYP GGA energy functional with high integral accuracy. Finally, an experimental assembly for obtention of amino acids and polypeptides is proposed. Brief, the three initial syntones: CH2, NH and CO, in nitrogen form aziridinone. That, in reactions with the same three syntones form, the more structured syntone precursors of proteinogenic amino acids and polypeptides. At the contact with primary atmosphere components are formed the first proteinogenic amino acids and polypeptides. The first polypeptides appear from polypeptide precursors and not from proteinogenic amino acids.

The guanylated bioamine agmatine, H 2 N ( CH 2 ) 4 N C ( NH 2 ) 2 ⇌ H 2 N ( CH 2 ) 4 NH C ( NH 2 ) NH , formed by decarboxylation of the proteinogenic amino acid arginine, plays an important role in the physiological processes of living organisms. Its structure is marked by the flexibility of the four-carbon chain connecting the two potentially basic amino and guanidino sites. Owing to these noteworthy properties and the questionable literature data on its protonated forms, its structure and intrinsic basicity were carefully scrutinized at the B3LYP/6–311+G(d,p) level. Three types of isomerism (prototropy and geometrical isomerism of the guanidino group, and rotational isomerism of the chain) were considered in this structural investigation. Various tautomers, as well as E/Z-isomers of the free guanidino group, various coiled and open conformations of the alkyl chain, and potential protonation sites (alkylamino and guanidine imino) were analyzed. Due to n-π conjugation in the guanidino group, its amino nitrogen (erroneously taken in the literature as the site of monoprotonation) is the least probable candidate as a protonation site. The H2N(CH2)4 N C(NH2)2 tautomer slightly predominates in the tautomeric mixture. One of its coiled conformations, facilitating the formation of an internal hydrogen-bond, possesses the lowest enthalpy, whereas one of its open conformations has the lowest Gibbs energy. The guanidine imino-nitrogen is without any doubt the favored site of protonation in the gas phase and in solution. Monoprotonated agmatine prefers the coiled conformations, all stabilized by intramolecular H-bonding, in a scorpion-shaped arrangement. The DFT-estimated PA of agmatine is higher than the experimental PAs reported for other bidentate bioamines (cadaverine, putrescine, and histamine) and close to that of the superbasic bicyclic guanidine MTBD. A guanylation of one amino group of diamines (NH2 in putrescine or NMe2 in tetramethyldiamines) increases their PA by ca. 60 kJ mol−1.

The proteinogenic amino acid l-serine is a precursor for various essential biomolecules in all organisms. 3-Phosphoglycerate dehydrogenase (PGDH) is the first committed enzyme of the phosphorylated pathway of l-serine biosynthesis, and is regulated by negative feedback from l-serine in bacteria and plants. In the present study, two Arabidopsis PGDH isoforms were inhibited by l-serine but were activated by l-amino acids such as l-homocysteine in vitro. Activation and inhibition by these amino acids was cooperative, suggesting an allosteric mechanism. Moreover, the half maximal effective concentration of l-homocysteine was 2 orders of magnitude lower than that of l-serine, suggesting greater regulatory potency. These are the first data to show that PGDH is activated by various biomolecules and indicate that serine biosynthesis is regulated by multiple pathways.

Stereoselective high-performance liquid chromatographic and subcritical fluid chromatographic separations of 19 Nα-Fmoc proteinogenic amino acid enantiomers were carried out by using Quinidine-based zwitterionic and anion-exchanger-type chiral stationary phases Chiralpak ZWIX(−) and QD-AX. For optimization of retention and enantioselectivity, the ratio of bulk solvent components (MeOH/MeCN, H2O/MeOH, or CO2/MeOH) and the nature and concentration of the acid and base additives (counter- and co-ions) were systematically varied. The effect of column temperature on the enantioseparation was investigated and thermodynamic parameters were calculated from the van't Hoff plots ln α vs. 1/T. The thermodynamic parameters revealed that the enantioseparations were enthalpy-driven. The elution sequence was determined in all cases and with the exception of Fmoc-Cys(Trt)-OH, it was identical on both chiral stationary phases whereby the L-enantiomers eluted before the D-enantiomers.

Selenium deficiency in various degrees affects around 15% of the world’s population, contributing to a variety of health problems. In this study, we examined the accumulation and biotransformation of soil applied Se-supplementation (sodium selenite and sodium selenate forms) at different concentrations, along with growth and yield formation of green pea, in a greenhouse experiment. Biotransformation of inorganic Se was evaluated using HPLC-ICP-MS for Se-species separation in the above ground parts of green pea. Results showed 3 mg kg−1 SeIV increased green pea growth biomarkers and also caused an increase in protein content in leaves by 17%. Selenomethionine represented 65% of the total selenium content in shoots, but was lower in pods and seeds (54 and 38%, respectively). Selenomethionine was the major species in all plant parts and the only organic selenium form in the lower SeIV concentration range. Elevating the dose of SeIV (≥30 mg kg−1) triggered detrimental effects on growth and protein content and caused higher accumulation of inorganic Se in forms of SeVI and SeIV. Selenocysteine, another organic form of proteinogenic amino acid, was determined when SeIV (≥10 mg kg−1) was applied in higher concentrations. Thus, agronomic biofortification using the appropriate chemical form and concentration of Se will have positive effects on green pea growth and its enriched shoots and seeds provide a value-added protein source for livestock and humans with significant increased selenomethionine.

Despite their biological importance, post-translationally modified proteins are notoriously difficult to produce in a homogeneous fashion using conventional expression systems. Chemical protein synthesis or semi-synthesis offers a solution to this problem; however, traditional strategies often rely on sulfur-based chemistry that is incompatible with the presence of multiple cysteine residues in the target protein. To overcome these limitations, we present the design and synthesis of γ-selenolysine, a selenol-containing form of the commonly modified proteinogenic amino acid, lysine. The utility of γ-selenolysine is demonstrated with the traceless ligation of the small ubiquitin-like modifier protein, SUMO-1, to a peptide segment of human glucokinase. The resulting polypeptide is poised for native chemical ligation and selective deselenization in the presence of unprotected cysteine residues. Selenolysine’s straightforward synthesis and incorporation into synthetic peptides marks it as a universal handle for conjugating any ubiquitin-like modifying protein to its target.

© 2019, Springer-Verlag GmbH Austria, part of Springer Nature. In addition to the 20 protein amino acids that are vital to human health, hundreds of naturally occurring amino acids, known as non-proteinogenic amino acids (NPAAs), exist and can enter the human food chain. Some NPAAs are toxic through their ability to mimic protein amino acids and this property is utilised by NPAA-containing plants to inhibit the growth of other plants or kill herbivores. The NPAA l-azetidine-2-carboxylic acid (Aze) enters the food chain through the use of sugar beet (Beta vulgaris) by-products as feed in the livestock industry and may also be found in sugar beet by-product fibre supplements. Aze mimics the protein amino acid l-proline and readily misincorporates into proteins. In light of this, we examined the toxicity of Aze to mammalian cells in vitro. We showed decreased viability in Aze-exposed cells with both apoptotic and necrotic cell death. This was accompanied by alterations in endosomal–lysosomal activity, changes to mitochondrial morphology and a significant decline in mitochondrial function. In summary, the results show that Aze exposure can lead to deleterious effects on human neuron-like cells and highlight the importance of monitoring human Aze consumption via the food chain.

Spent yeast from beer manufacturing is a cost-effective and nutrient-rich starting material for the production of yeast extracts. In this study, it is shown how physiologically important ingredients in a yeast extract are influenced by the composition of the spent yeast from the brewing process. In pilot fermentations, the time of cropping (primary fermentation, lagering) of the spent yeast and the original gravity (12 ˚P, 16 ˚P, 20 ˚P) of the fermentation medium was varied, and four alternative non-Saccharomyces yeast strains were compared with two commercial Saccharomyces yeast strains. In addition, spent yeast was contaminated with the beer spoiler Lactobacillus brevis. The general nutrient composition (total protein, fat, ash) was investigated as well as the proteinogenic amino acid spectrum, the various folate vitamers (5-CH3-H4folate, 5-CHO-H4folate, 10-CHO-PteGlu, H4folate, PteGlu) and the biological activity (reduction, antioxidative potential) of a mechanically (ultrasonic sonotrode) and an autolytically produced yeast extract. All the investigated ingredients from the yeast extract were influenced by the composition of the spent yeast from the brewing process. The biodiversity of the spent yeast from the brewing process therefore directly affects the content of physiologically valuable ingredients of a yeast extract and should be taken into consideration in industrial manufacturing processes.

The substrate profile of peptiligase, a stable enzyme designed for peptide ligation in aqueous environments, was mapped using six different peptide libraries. The most discriminating substrate binding pocket proved to be the first nucleophile binding subsite (S1), which is crucial for the peptide ligation yield. Two important amino acids shaping the S1 pocket are M213 and L208. A site-saturation library of the M213 position yielded two variants with a significantly broadened substrate profile, i.e., M213G and M213P. Next, examination of two libraries with M213G+L208X and M213P+L208X (with X being any proteinogenic amino acid) resulted in a toolbox of enzymes which can accommodate any proteinogenic amino acid in the S1 pocket, except proline. The applicability of a particular enzyme variant in chemoenzymatic peptide synthesis was demonstrated by coupling at the gram scale of two peptide segments to yield exenatide, a 39-mer therapeutic peptide used in the treatment of diabetes type II. The overall yield of 43% is at least 2-fold higher than yields reported for conventional syntheses of exenatide by full solid-phase peptide synthesis; large-scale production costs are expected to be significantly reduced if the enzymatic coupling process is employed to manufacture this peptide.

L-tyrosine (Tyr) plays a crucial role as a proteinogenic amino acid and also as a precursor to several neurotransmitters and hormones. Here we demonstrate coloration of Tyr based on organic-semiconductor interfacial charge-transfer (ICT) transitions. The ICT transitions from Tyr to TiO 2 are induced by the chemisorption of Tyr on TiO 2 surfaces via the hydroxy group of the phenol moiety. Because other amino acids possess no chemical group to induce ICT transitions, this coloration method enables to detect Tyr selectively without drastic structural change in contrast to the conventional coloration methods.

Selenocysteine is the only proteinogenic amino acid encoded by a recoded in-frame UGA codon that does not operate as the canonical opal stop codon. A specialized translation elongation factor, eEFSec in eukaryotes and SelB in prokaryotes, promotes selenocysteine incorporation into selenoproteins by a still poorly understood mechanism. Our structural and biochemical results reveal that four domains of human eEFSec fold into a chalice-like structure that has similar binding affinities for GDP, GTP and other guanine nucleotides. Surprisingly, unlike in eEF1A and EF-Tu, the guanine nucleotide exchange does not cause a major conformational change in domain 1 of eEFSec, but instead induces a swing of domain 4. We propose that eEFSec employs a non-canonical mechanism involving the distinct C-terminal domain 4 for the release of the selenocysteinyl-tRNA during decoding on the ribosome., Specialized translation elongation factors (eEFSec and SelB) promote selenocysteine incorporation into proteins. Here, the authors report the structure of human eEFSec, examine its interactions with guanine nucleotides, and propose a non-canonical mechanism for decoding selenocysteine.

Selenocysteine is the 21st proteinogenic amino acid in mammals. The human genome contains 25 genes encoding selenoproteins, and their significance for human health is increasingly recognized through the identification of patients with inborn errors in selenoprotein biosynthetic factors or in individual selenoproteins. Mutations in selenoprotein N (SEPN1) lead to a spectrum of disorders collectively called SEPN1-related myopathy, and mutations in glutathione peroxidase 4 (GPX4) cause respiratory failure and bone defects, and mutations in thioredoxin reductase 2 (TXNRD2) are associated with familial glucocorticoid deficiency. Pathogenic mutations in selenocysteine synthase (SEPSECS) cause neurodevelopmental disorders, but also other factors epistatic to selenoprotein biosynthesis, such as SECIS-binding protein 2 (SECISBP2) and tRNA

Understanding the adsorption, film growth mechanisms, and hydrogen bonding interactions of biological molecules on semiconductor surfaces has attracted much recent attention because of their applications in biosensors, biocompatible materials, and biomolecule-based electronic devices. One of the most challenging questions when studying the behavior of biomolecules on a metal or semiconductor surface is "What are the driving forces and film growth mechanisms for biomolecular adsorption on these surfaces?" Despite a large volume of work on self-assembly of amino acids on single-crystal metal surfaces, semiconductor surfaces offer more direct surface-mediated interactions and processes with biomolecules. This is due to their directional surface dangling bonds that could significantly perturb hydrogen bonding arrangements. For all the proteinogenic biomolecules studied to date, our group has observed that they generally follow a "universal" three-stage growth process on Si(111)7×7 surface. This is supported by corroborating data obtained from a three-pronged approach of combining chemical-state information provided by X-ray photoelectron spectroscopy (XPS) and the site-specific local density-of-state images obtained by scanning tunneling microscopy (STM) with large-scale quantum mechanical modeling based on the density functional theory with van der Waals corrections (DFT-D2). Indeed, this three-stage growth process on the 7×7 surface has been observed for small benchmark biomolecules, including glycine (the simplest nonchiral amino acid), alanine (the simplest chiral amino acid), cysteine (the smallest amino acid with a thiol group), and glycylglycine (the smallest (di)peptide of glycine). Its universality is further validated here for the other sulfur-containing proteinogenic amino acid, methionine. We use methionine as an example of prototypical proteinogenic amino acids to illustrate this surface-mediated process. This type of growth begins with the formation of a covalent-bond driven interfacial layer (first adlayer), followed by that of a transitional layer driven by interlayer and intralayer hydrogen bonding (second adlayer), and then finally the zwitterionic multilayers (with intralayer hydrogen bonding). The important role of surface-mediated hydrogen bonding as the key for this universal three-stage growth process is demonstrated. This finding provides new insight into biomolecule-semiconductor surface interactions often found in biosensors and biomolecular electronic devices. We also establish the trends in the H-bond length among different types of the hydrogen bonding for dimolecular structures in the gas phase and on the Si(111)7×7 surface, the latter of which could be validated by their STM images. Finally, five simple rules of thumb are developed to summarize the adsorption properties of these proteinogenic biomolecules as mediated by hydrogen bonding, and they are expected to provide a helpful guide to future studies of larger biomolecules and their potential applications.

A systematic investigation regarding the application of catalytic amounts of all 20 proteinogenic amino acids in the homo aldol condensation of aldehydes is described obtaining excellent yields of the desired α,β-unsaturated aldehyde. These investigations proved the basic amino acids, lysine and arginine, are effective as organocatalysts, if comparably low concentrations are applied. Through the stepwise and systematic condition alteration, the reaction could be optimised and successfully transferred to other substrates with longer, branched or functionalised alkyl chains. The highest yields are observed with tryptophan as organocatalyst in only 1 h reaction time with TONs of up to 27.

Plants have sophisticated stress-sensing and stress-coping mechanisms which enable them to survive and be productive under abiotic and biotic stress conditions. According to the type and severity of the stress, different adaptive and/or tolerance mechanisms are involved in defense processes. However, these processes may overlap or be active together in order to make it easier for plants to fight against different or combined stresses in their natural environment at the same time. Osmotic adjustment and protection of membrane integrity are the two important and mutual components of overall defense processes. The bioactive molecules, glycinebetaine, trehalose, and proline, have been reported to maintain both osmotic adjustment and membrane integrity either by exogenous treatments or by their increased biosynthesis. Glycinebetaine is a quaternary ammonium molecule which is well-known to be a compatible solute. Trehalose is a non-reducing disaccharide with water replacement and glass formation characteristics. The proteinogenic amino acid proline is also a compatible osmoprotectant molecule with a variety of stress-related functions. Although there is a vast amount of information available on the protective role of these molecules, their mode of action is still unclear. Differentiation in the expression of defense-related genes is usually found out to be correlated with the increased or decreased levels of these molecules. Here we collected and reviewed the latest information available on glycinebetaine, trehalose, and proline by means of their influence and impact on the transcription and regulation of the stress-responsive genes.