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Abstract Viridin and viridiol, along with wortmannin, metabolized by filamentous fungus Trichoderma virens, are identical furanosteroids with high-potent inhibitory activity towards phosphatidylinositol 3-kinase (PI3K) that associates the growth of tumor cells. Therefore, structure–activity relationship study (SAR) of these furanosteroids contributes to the development of novel drugs. However, rational supply methods have not been established yet. In this study, we generated an efficient method to produce both viridin and viridiol by using a unique pH regulated T. virens culture manner. Besides, we successfully obtained β-viridin (epimer of viridin) crystal and X-ray structure, of which the CAS number was registered without stereochemistry. Furthermore, applying the original method to stable isotope study, we also obtained [U-13C]-viridn and [U-13C]-viridol by using [U-13C6]-glucose as a carbon source replacing normal glucose which can be used to elucidate the biosynthesis pathway of furanosteroids.

Antimicrobial resistance has emerged as a significant danger to global health, and the need for more effective antimicrobial resistance (AMR) control has been highlighted. Cinnamic acid is abundant in plant products and is a potential starting material for further modification, focusing on the development of new antimicrobial compounds. In the following review, we describe the classification of critical antibacterial-guided reactions applied to the main skeleton structure of cinnamic acid derivatives over the last decade. Of all of the main parts of cinnamic acids, the phenyl ring and the carboxylic group significantly affect antibacterial activity. The results presented in the following review can provide valuable insights into considerable features in the organic modification of cinnamic acids related to antibacterial medication development and the food industry.

ABSTRACT Strains of the Ralstonia solanacearum species complex (RSSC), although known as the causative agent of bacterial wilt disease in plants, induce the chlamydospores of many fungal species and invade them through the spores. The lipopeptide ralstonins are the chlamydospore inducers produced by RSSC and are essential for this invasion. However, no mechanistic investigation of this interaction has been conducted. In this study, we report that quorum sensing (QS), which is a bacterial cell-cell communication, is important for RSSC to invade the fungus Fusarium oxysporum (Fo). ΔphcB, a deletion mutant of QS signal synthase, lost the ability to both produce ralstonins and invade Fo chlamydospores. The QS signal methyl 3-hydroxymyristate rescued these disabilities. In contrast, exogenous ralstonin A, while inducing Fo chlamydospores, failed to rescue the invasive ability. Gene-deletion and -complementation experiments revealed that the QS-dependent production of extracellular polysaccharide I (EPS I) is essential for this invasion. The RSSC cells adhered to Fo hyphae and formed biofilms there before inducing chlamydospores. This biofilm formation was not observed in the EPS I- or ralstonin-deficient mutant. Microscopic analysis showed that RSSC infection resulted in the death of Fo chlamydospores. Altogether, we report that the RSSC QS system is important for this lethal endoparasitism. Among the factors regulated by the QS system, ralstonins, EPS I, and biofilm are important parasitic factors. IMPORTANCE Ralstonia solanacearum species complex (RSSC) strains infect both plants and fungi. The phc quorum-sensing (QS) system of RSSC is important for parasitism on plants, because it allows them to invade and proliferate within the hosts by causing appropriate activation of the system at each infection step. In this study, we confirm that ralstonin A is important not only for Fusarium oxysporum (Fo) chlamydospore induction but also for RSSC biofilm formation on Fo hyphae. Extracellular polysaccharide I (EPS I) is also essential for biofilm formation, while the phc QS system controls these factors in terms of production. The present results advocate a new QS-dependent mechanism for the process by which a bacterium invades a fungus.

Patients with a ruptured abdominal aortic aneurysm (rAAA) still have high mortality. Rapid diagnosis and treatment are vital for improving survival outcomes. rAAA management has evolved regarding these factors. We have reported the case of a 70-year-old man with an rAAA that was rapidly diagnosed and treated in a hybrid emergency room (ER). A hybrid ER is an integrated ER capable of computed tomography scanning, interventional radiology, and surgery in one place. In the present case, the door-to-intervention time was 35 minutes. The use of hybrid ERs has the potential to enhance the speed and quality of diagnostic and definitive treatment of rAAAs.

In materials (polymer) science and medicinal chemistry, heteroaromatic derivatives play the role of the central skeleton in development of novel devices and discovery of new drugs. On the other hand, (3-trifluoromethyl)phenyldiazirine (TPD) is a crucial chemical method for understanding biological processes such as ligand–receptor, nucleic acid–protein, lipid–protein, and protein–protein interactions. In particular, use of TPD has increased in recent materials science to create novel electric and polymer devices with comparative ease and reduced costs. Therefore, a combination of heteroaromatics and (3-trifluoromethyl)diazirine is a promising option for creating better materials and elucidating the unknown mechanisms of action of bioactive heteroaromatic compounds. In this review, a comprehensive synthesis of (3-trifluoromethyl)diazirine-substituted heteroaromatics is described.

Introduction: In rectal cancer, distal intramural spread may sometimes occur, but a maximum extent of distal spread of > 6 cm is very rare. Case Presentation: A 65-year-old Japanese male with an advanced rectal cancer tumor with para-aortic lymph node metastasis was admitted. We performed a low anterior resection with lymphadenectomy, but the intraoperative frozen-section analysis of margins revealed malignant cell positivity; we, therefore, performed an abdominoperineal resection. Pathological findings showed that the maximum extent of distal spread was 6 cm. After 12 courses of FOLFOX4 as adjuvant chemotherapy, abdominal computed tomography revealed whole lymph node metastases, including Virchow’s node. Though FOLFIRI + panitumumab was started, he was not eligible for additional chemotherapy after 10 cycles. Conclusion: An intraoperative frozen pathology examination was helpful for the additional resection, when unexpected distal spreading had occurred in rectal cancer. The evidence of a distal negative margin should not be underestimated.

Neuroendocrine carcinoma (NEC) of the colon is very rare, and squamous cell carcinoma (SCC) of colon cancer is rare. We recently treated a patient with both NEC and SCC that initially presented as multiple unresectable liver and lung metastases. A 68-year-old Japanese man was referred to our hospital because of diarrhea with descending colon cancer obstruction. He underwent a left colectomy. Based on immunohistochemistry results, we diagnosed mixed NEC and SCC, the primary lesion location of which was probably the lung in the final pathologic examination. He began systemic palliative chemotherapy with CDDP and CPT-11. After 3 months of treatment, shown the progressive disease, we started CDDP and VP-16. The patient was not eligible for additional chemotherapy after 2 months.

This review focuses on diaziridine, a high strained three-membered heterocycle with two nitrogen atoms that plays an important role as one of the most important precursors of diazirine photoaffinity probes, as well as their formation and transformation. Recent research trends can be grouped into three categories, based on whether they have examined non-substituted, N-monosubstituted, or N,N-disubstituted diaziridines. The discussion expands on the conventional methods for recent applications, the current spread of studies, and the unconventional synthesis approaches arising over the last decade of publications.

Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb “Manshanfong” used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum, is a meroterpenoid with antibacterial, anti-HIV, and anti-inflammatory activities. However, the mechanisms underlying these pharmacologic activities are poorly understood. To develop new drugs based on DCA, more information is required regarding its interactions with biomolecules. The present study showed that DCA inhibits the activity of the enzyme sphingomyelin synthase, with an IC50 of 4 µM. The structure–activity relationships between DCA and sphingomyelin synthase were evaluated using derivatives and cyclized hongoquercin A. In addition, DCA was found to inhibit amyloid β aggregation. These results may help in the design of effective drugs based on DCA.

In this study, a one-degree-of-freedom myoelectric prosthesis system was proposed using a Parent Wireless Assistive Interface (PWAI) that allowed an external assistant (e. g., the parent of the user) to immediately adjust the parameters of the prosthetic hand controller. In the PWAI, the myoelectric potential of use of the upper limb was plotted on an external terminal in real time. Simultaneously, the assistant adjusted the parameters of the prosthetic hand control device and manually manipulated the prosthetic hand. With these functions, children that have difficulty verbally communicating could obtain properly adjusted prosthetic hands. In addition, non-experts could easily adjust and manually manipulate the prosthesis; therefore, training for the prosthetic hands could be performed at home. Two types of hand motion discrimination methods were constructed in this study of the myoelectric control system: (1) a threshold control based on the myoelectric potential amplitude information and (2) a pattern recognition of the frequency domain features. In an evaluation test of the prosthesis threshold control system, child subjects achieved discrimination rates as high as 89%, compared with 96% achieved by adult subjects. Furthermore, the high discrimination rate was maintained by sequentially updating the threshold value. In addition, a discrimination rate of 82% on average was obtained by recognizing three motions using the pattern recognition method.

Sphingoid base derivatives have attracted increasing attention as promising chemotherapeutic candidates against lifestyle diseases such as diabetes and cancer. Natural sphingoid bases can be a potential resource instead of those derived by time-consuming total organic synthesis. In particular, glucosylceramides (GlcCers) in food plants are enriched sources of sphingoid bases, differing from those of animals. Several chemical methodologies to transform GlcCers to sphingoid bases have already investigated; however, these conventional methods using acid or alkaline hydrolysis are not efficient due to poor reaction yield, producing complex by-products and resulting in separation problems. In this study, an extremely efficient and practical chemoenzymatic transformation method has been developed using microwave-enhanced butanolysis of GlcCers and a large amount of readily available almond β-glucosidase for its deglycosylation reaction of lysoGlcCers. The method is superior to conventional acid/base hydrolysis methods in its rapidity and its reaction cleanness (no isomerization, no rearrangement) with excellent overall yield.

Konjac ceramide (kCer) is a plant-type ceramide composed of various long-chain bases and α-hydroxyl fatty acids. The presence of d4t,8t-sphingadienine is essential for semaphorin 3A (Sema3A)-like activity. Herein, we examined the three neuropilin 1 (Nrp1) domains (a1a2, b1b2, or c), and found that a1a2 binds to d4t,8t-kCer and possesses Sema3A-like activity. kCer binds to Nrp1 with a weak affinity of μM dissociation constant (Kd). We wondered whether bovine serum albumin could influence the ligand−receptor interaction that a1a2 has with a single high affinity binding site for kCer (Kd in nM range). In the present study we demonstrated the influence of bovine serum albumin. Thermal denaturation indicates that the a1a2 domain may include intrinsically disordered region (IDR)-like flexibility. A potential interaction site on the a1 module was explored by molecular docking, which revealed a possible Nrp1 activation mechanism, in which kCer binds to Site A close to the Sema3A-binding region of the a1a2 domain. The a1 module then accesses a2 as the IDR-like flexibility becomes ordered via kCer-induced protein rigidity of a1a2. This induces intramolecular interaction between a1 and a2 through a slight change in protein secondary structure.

Aryl-keto-containing α-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl α-amino acids, nonproteinogenic α-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing α-amino acids by Friedel-Crafts acylation using acidic α-amino acids as acyl-donors and Lewis acids or Brönsted acids as catalysts.

Photoaffinity labeling is a reliable analytical method for biological functional analysis. Three major photophores—aryl azide, benzophenone and trifluoromethyldiazirine—are utilized in analysis. Photophore-bearing l-phenylalanine derivatives, which are used for biological functional analysis, were inoculated into a Klebsiella sp. isolated from the rhizosphere of a wild dipterocarp sapling in Central Kalimantan, Indonesia, under nitrogen-limiting conditions. The proportions of metabolites were quite distinct for each photophore. These results indicated that photophores affected substrate recognition in rhizobacterial metabolic pathways, and differential photoaffinity labeling could be achieved using different photophore-containing l-phenylalanine derivatives.

Squalene is a triterpenoid compound and widely used in various industries such as medicine and cosmetics due to its strong antioxidant and anticancer properties. The purpose of this study is to increase the accumulation of squalene in filamentous fungi using exogeneous butenafine hydrochloride, which is an inhibitor for squalene epoxidase. The detailed settings achieved that the filamentous fungi, Trichoderma virens PS1-7, produced squalene up to 429.93 ± 51.60 mg/L after culturing for 7 days in the medium consisting of potato infusion with glucose at pH 4.0, in the presence of 200 μm butenafine. On the other hand, no squalene accumulation was observed without butenafine. This result indicated that squalene was biosynthesized in the filamentous fungi PS1-7, which can be used as a novel source of squalene. In addition, we successfully obtained highly 13C-enriched squalene by using [U-13C6]-glucose as a carbon source replacing normal glucose. [ABSTRACT FROM AUTHOR]

Ralstonia solanacearum has an orphan hybrid polyketide synthase-nonribosomal peptide synthetase gene cluster. We herein isolate its products (named ralstonins A and B) from R. solanacearum and elucidate their structures and biological activities. Ralstonins are unusual lipodepsipeptides composed of 11 amino acids (containing unique amino acids such as β-hydroxytyrosine and dehydroalanine) and a 3-amino-2-hydroxyoctadecanoic acid, and their production is controlled by quorum sensing, a mechanism of bacterial cell-cell communication. Ralstonins exhibited chlamydospore-inducing activity and phytotoxicity. [ABSTRACT FROM AUTHOR]

5-Nitro-2-propoxyaniline is one of the strongest artificial sweeteners. However, little is known about the detailed relationship of the structure and biological activity between 5-nitro-2-propoxyaniline and its sweet receptor. Photoaffinity labeling is a useful method for revealing interactions of a small bioactive compound with molecules. Therefore, we synthesized photoreactive 2-propoxyaniline derivatives as useful tools for revealing the interactions by photoaffinity labeling. [ABSTRACT FROM AUTHOR]

Serine palmitoyltransferase (SPT) catalyzes the pyridoxal-50-phosphate (PLP)-dependent decarboxylative condensation of Lserine and palmitoyl-CoA to form 3-ketodihydrosphingosine (KDS). Although SPT was shown to synthesize corresponding products from amino acids other than L-serine, it is still arguable whether SPT catalyzes the reaction with D-serine, which is a question of biological importance. Using high substrate and enzyme concentrations, KDS was detected after the incubation of SPT from Sphingobacterium multivorum with D-serine and palmitoyl-CoA. Furthermore, the KDS comprised equal amounts of 2S and 2R isomers. ¹H-NMR study showed a slow hydrogen-deuterium exchange at Cα of serine mediated by SPT. We further confirmed that SPT catalyzed the racemization of serine. The rate of the KDS formation from D-serine was comparable to those for the α-hydrogen exchange and the racemization reaction. The structure of the D-serine-soaked crystal (1.65 Å resolution) showed a distinct electron density of the PLP-L-serine aldimine, interpreted as the racemized product trapped in the active site. The structure of the α-methyl-Dserine-soaked crystal (1.70 Å resolution) showed the PLP-α-methyl-D-serine aldimine, mimicking the D-serine-SPT complex prior to racemization. Based on these enzymological and structural analyses, the synthesis of KDS from D-serine was explained as the result of the slow racemization to L-serine, followed by the reaction with palmitoyl-CoA, and SPT would not catalyze the direct condensation between D-serine and palmitoyl-CoA. It was also shown that the S. multivorum SPT catalyzed the racemization of the product KDS, which would explain the presence of (2R)-KDS in the reaction products. [ABSTRACT FROM AUTHOR]

The article presents a research papers analyzing hydrogen/deuterium exchange (H/D exchange) of cross-linkable a-amino acid derivatives with deuterated trifluoromethanesulfonic acid (TfOD).Topics discussed include exchange of a partial H/D for trifluoromethyldiazirinyl (TFMD) phenylalanine derivatives, biological functions of bioactive peptides and proteins, and mass spectrum compared to untreated samples.

Serine palmitoyltransferase (SPT) is a key enzyme of sphingolipid biosynthesis, which catalyzes the pyridoxal-50-phosphate-dependent decarboxylative condensation reaction of L-serine (L-Ser) and palmitoyl-CoA (PalCoA) to form 3-ketodihydrosphingosine called long chain base (LCB). SPT is also able to metabolize L-alanine (L-Ala) and glycine (Gly), albeit with much lower efficiency. Human SPT is a membranebound large protein complex containing SPTLC1/SPTLC2 heterodimer as the core subunits, and it is known that mutations of the SPTLC1/SPTLC2 genes increase the formation of deoxy-type of LCBs derived from L-Ala and Gly to cause some neurodegenerative diseases. In order to study the substrate recognition of SPT, we examined the reactivity of Sphingobacterium multivorum SPT on various amino acids in the presence of PalCoA. The S. multivorum SPT could convert not only L-Ala and Gly but also L-homoserine, in addition to L-Ser, into the corresponding LCBs. Furthermore, we obtained highquality crystals of the ligand-free form and the binary complexes with a series of amino acids, including a nonproductive amino acid, L-threonine, and determined the structures at 1.40 to 1.55 Å resolutions. The S. multivorum SPT accommodated various amino acid substrates through subtle rearrangements of the active-site amino acid residues and water molecules. It was also suggested that non-active-site residues mutated in the human SPT genes might indirectly influence the substrate specificity by affecting the hydrogen-bonding networks involving the bound substrate, water molecules, and amino acid residues in the active site of this enzyme. Collectively, our results highlight SPT structural features affecting substrate specificity for this stage of sphingolipid biosynthesis. [ABSTRACT FROM AUTHOR]

Indole-3-propionic acid (IPA), a member of the plant auxin family, plays an important role in biological activity. There are few reports on the preparation of deuterated IPA. Deuterated trifluoromethanesulfonic acid (TfOD) is a hydrogen-deuterium exchange reagent used for aromatic compounds. The hydrogen-deuterium exchange of IPA and indole-3-alaknoic acid derivatives with TfOD was examined in detail. [ABSTRACT FROM AUTHOR]