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Phenyl polyenes comprise a small family of bacterial natural products with broad and potent bioactivities, primarily found in actinobacteria. Here we report the discovery of five new phenyl polyene metabolites, maduraflavacins A-E ( 1 - 5 ), from a rare, marine-derived actinobacteria strain Actinomadura glauciflava NA03286. The structures of these natural products were determined by NMR spectroscopy, HRESIMS, LC-MS/MS, and chemical derivatization. All of these new maduraflavacins feature methyl substitutions at the polyene side chain, and maduraflavacins A-C ( 1 - 3 ) possessed a 1- N -β-d-glucosamine-(3 → 1)- O -β-d-glucopyranosyl-(3 → 1)- O -β-d-glucopyranosyl-(6 → 1)- O -β-d-glucopyranoside tetrasaccharide moiety via an amido linkage with a phenyl polyene skeleton. Compounds 1 and 2 showed weak antibacterial activities against the Gram-positive bacteria Staphylococcus aureus Sau 16339 and Micrococcus luteus , respectively.

Prymnesium parvum are harmful haptophyte algae that cause massive environmental fish kills. Their polyketide polyether toxins, the prymnesins, are among the largest nonpolymeric compounds in nature and have biosynthetic origins that have remained enigmatic for more than 40 years. In this work, we report the "PKZILLAs," massive P. parvum polyketide synthase (PKS) genes that have evaded previous detection. PKZILLA-1 and -2 encode giant protein products of 4.7 and 3.2 megadaltons that have 140 and 99 enzyme domains. Their predicted polyene product matches the proposed pre-prymnesin precursor of the 90-carbon-backbone A-type prymnesins. We further characterize the variant PKZILLA-B1, which is responsible for the shorter B-type analog prymnesin-B1, from P. parvum RCC3426 and thus establish a general model of haptophyte polyether biosynthetic logic. This work expands expectations of genetic and enzymatic size limits in biology.

Plastic waste, especially positively buoyant polymers known as polyolefins, are a major component of floating debris in the marine environment. While plastic colonisation by marine microbes is well documented from environmental samples, the succession of marine microbial community structure over longer time scales (> > 1 month) and across different types and shapes of plastic debris is less certain. We analysed 16S rRNA and 18S rRNA amplicon gene sequences from biofilms on polyolefin debris floating in a flow-through seawater tank in Hawai'i to assess differences in microbial succession across the plastic types of polypropylene (PP) and both high-density polyethylene (HDPE) and low-density polyethylene (LDPE) made of different plastic shapes (rod, film and cube) under the same environmental conditions for 1 year. Regardless of type or shape, all plastic debris were dominated by the eukaryotic diatom Nitzschia, and only plastic type was significantly important for bacterial community structure over time (p = 0.005). PE plastics had higher differential abundance when compared to PP for 20 bacterial and eight eukaryotic taxa, including the known plastic degrading bacterial taxon Hyphomonas (p = 0.01). Results from our study provide empirical evidence that plastic type may be more important for bacterial than eukaryotic microbial community succession on polyolefin pollution under similar conditions., (© 2024 The Author(s). Environmental Microbiology Reports published by John Wiley & Sons Ltd.)

Coordinative chain transfer polymerization (CCTP) of ethylene and its copolymerization with 1,3-butadiene is conducted in toluene at 80 °C using a combination of {(Me 2 Si(C 13 H 8 ) 2 )Nd(μ-BH 4 )[(μ-BH 4 )Li(THF)]} 2 (1) metal complex and various organomagnesium compounds used as chain transfer agents including n-butyl-n-octyl-magnesium (BOMAG), n-butyl-mesityl-magnesium (n-BuMgMes), n-butyl-magnesium chloride (n-BuMgCl), n-pentyl-magnesium bromide (n-C 5 H 11 MgBr), pentanediyl-1,5-di(magnesium bromide) (PDMB) and isobutyl-magnesium chloride (i-BuMgCl). Kinetics and performance in terms of control of the (co)polymerization are comparatively discussed particularly considering the presence of ether and the nature of the organomagnesium compounds employed. Taking advantage of the well-known reactivity between nitrile and molecular organomagnesium compounds, the functionalization of the chains is further carried out by deactivation of the polymerization medium with benzonitrile or methoxybenzonitrile compounds leading to ketone ω-functionalized chains. The success of the functionalizations is extended to coupling strategies using dinitrile reagents and to the functionalization of high molar mass ethylene butadiene rubber (EBR)., (© 2024 Wiley‐VCH GmbH.)

This communication reports an effective strategy helping address the long-troubling melt processing issue of isotactic polybutene-1 (i-PB) caused by its extremely slow II-I crystal phase transition. The solution lies in a facile synthesis of i-PB containing H-shape long-chain-branching structures (LCB-i-PB) by applying a so-called ω-alkenylmethyldichlorosilane copolymerization-hydrolysis (ACH) chemistry to butene-1 polymerization with Ziegler-Natta or metallocene catalysts. It is evident that the H-shape LCB structures effectively enhance chain entanglements of i-PB and induce an over-the-board acceleration of the overall melt crystallization process including nucleation, form II crystallization, and form II-form I phase transition. As i-PB usually requires up to a week to reach equilibrium of the II-I phase transition, it is found that with LCB-i-PB such a transition is almost finished within as short as 24 h to even higher degrees., (© 2024 Wiley‐VCH GmbH.)

Polyene cyclizations are among the most complex and challenging transformations in biology. In a single reaction step, multiple carbon-carbon bonds, ring systems and stereogenic centres are constituted from simple, acyclic precursors 1-3 . Simultaneously achieving this kind of precise control over product distribution and stereochemistry poses a formidable task for chemists. In particular, the polyene cyclization of (3E,7E)-homofarnesol to the valuable naturally occurring ambergris odorant (-)-ambrox is recognized as a longstanding challenge in chemical synthesis 1,4-7 . Here we report a diastereoselective and enantioselective synthesis of (-)-ambrox and the sesquiterpene lactone natural product (+)-sclareolide by a catalytic asymmetric polyene cyclization by using a highly Brønsted-acidic and confined imidodiphosphorimidate catalyst in the presence of fluorinated alcohols. Several experiments, including deuterium-labelling studies, suggest that the reaction predominantly proceeds through a concerted pathway in line with the Stork-Eschenmoser hypothesis 8-10 . Mechanistic studies show the importance of the enzyme-like microenvironment of the imidodiphosphorimidate catalyst for attaining exceptionally high selectivities, previously thought to be achievable only in enzyme-catalysed polyene cyclizations., (© 2024. The Author(s).)

A new polyene macrolide, machidamycin (1), and a known compound YS-822A (2), were obtained by physicochemical screening from a culture broth of Streptomyces sp. K22-0017. The structures were elucidated using MS and 1D/2D NMR analyses. Compound 1 exhibited weak antifungal activity against Candida albicans and Mucor racemosus. Furthermore, 1 showed stronger antileishmanial activity than the existing drug paromomycin., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Silicone rubber tissue expanders and breast implants are associated with chronic inflammation, leading to the formation of fibrous capsules. If the inflammation is left untreated, the fibrous capsules can become hard and brittle and lead to formation of capsular contracture. When capsular contracture occurs, implant failure and reoperation is unavoidable. Fibrous capsule formation to medical grade silicone rubber breast implants and polyisobutylene-based electrospun fiber mats attached to silicone rubber with and without an anti-inflammatory therapeutic were compared. A linear polyisobutylene (PIB)-based thermoplastic elastomer is currently applied as a polymer coating for drug release on coronary stents to reduce restenosis. Recent work has created a drug releasing electrospun fiber mat from PIB-based materials. Important to this study, poly(alloocimene- b -isobutylene- b -alloocimene) (AIBA) was electrospun with zafirlukast (ZAF). ZAF is an anti-inflammatory drug that is able to reduce capsule formation and complications to silicone breast implants. Fiber mats are advantageous for local drug delivery because of their high porosity and surface area for drug release. The chief hypothesis was that local release of ZAF from AIBA would lower inflammatory signaling and resulting capsular formation after 90 days in vivo . Electrospun AIBA mats locally released ZAF, lowering inflammation and fibrous capsule development compared to medical grade silicone rubber. Locally and orally released ZAF led to similar results, but the former had much lower concentration that highlights local delivery's therapeutic potential. Released ZAF from AIBA fiber mats mitigated inflammation and serves as an alternative to existing clinical approaches.

The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces are introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (T c ) and shear temperature (T shear ) on crystallization and phase transition are explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high T c (105 °C). Besides, the shear-induced Form II can transit to Form I faster than the unsheared one. In addition, the phase transition rate increases as the T shear decreases, with the fastest rate occurring at T shear of 120 °C. The half transition time (t 1/2 ) is measured as 6.3 h when T c = 105 °C, T shear = 120 °C, which is much shorter than the 20.7 h required for unsheared samples. The accelerated phase transition of iPBu can be attributed to the stretching of molecular chains, resulting from shear treatment. This study provides a quantitative analysis of the influence of the shear treatment and the T shear on the II-I phase transition rate. It also presents a cost-effective and straightforward approach for expediting the phase transition process., (© 2024 Wiley‐VCH GmbH.)

Three types of starch with different amylose content were esterified and blended with polybutylene succinate (PBS) to obtain esterified manioc starch/PBS (EMS/PBS), esterified corn starch/PBS (ECS/PBS), and esterified waxy corn starch/PBS (EWS/PBS) composites. The EMS/PBS and ECS/PBS composites with high amylose content displayed typical V-type crystal structures. The original crystals of EWS, which had low amylose content, were disrupted during the esterification process. EWS exhibited the strongest interaction with PBS and the most favorable interface compatibility. The pyrolysis temperature was in order of EMS/PBS < ECS/PBS < EWS/PBS. The elongation at break of the three blends was higher than that of pure PBS. The esterification and plasticization of the EWS/PBS composite were the most comprehensive. The EWS/PBS composite showed the lowest storage modulus (G') and complex viscosity (η*). The interfacial bonding force of the composite materials increased with more amylopectin, decreasing intermolecular forces and destroying crystal structures, which decreased G' and η* and increased toughness. The EWS/PBS composite, with the least amylose content, had the best hydrophobicity and degradation performance.

There is a growing need for a mouthguard sheet material with higher shock absorption and dispersion capacity than those obtained by conventional materials. A five-layer mouthguard sheet material was previously developed using laminated ethylene vinyl acetate and polyolefin copolymer resin. In this study, the shock absorption capacity and dispersion capability of the new sheet material were investigated and compared with those of other materials. Impact testing for the new sheet material showed that the force required to displace the sheet by 1 mm was significantly higher at all thicknesses (p<0.001), whereas the puncture energy and displacement were significantly lower than those for ethylene vinyl acetate (p<0.05). The five-layer mouthguard sheet material successfully absorbed and resisted shock. Therefore, the sheet material potentially increases resistance to applied deformation in teeth and alveolar bone and maintains structure. The five-layer sheet material could expand the range of mouthguard products and help prevent oral trauma.

Polyolefins, composed of carbon and hydrogen atoms, dominate global polymer production. This stems from the wide range of physical and mechanical properties that various polyolefins can cover. Their versatile properties are largely tuned by chain microstructure, including molar mass distribution, comonomer content, and long-chain branching (LCB). Specifically, LCB imparts unique characteristics, notably enhances processability crucial for downstream applications. Tailoring LCB structural features has encouraged academic and industrial efforts, chronicle in this review from a chemistry standpoint. While encompassing post-reaction modification based traditional methods like peroxide grafting, ionizing beam irradiation, and coupling reactions, the main focus is given to catalyst-centric strategies and innovative polymerization schemes. The advent of single-site catalysts-metallocenes and late transition metals catalysts-amplifies interest in tailored chemical methods, but the progress in LCB formation flourishes via tandem catalytic systems and bimetallic catalysts under controlled reaction conditions. Specifically, the breakthrough in coordinative chain transfer polymerization unveils a novel avenue for controlled LCB synthesis by sequential chain propagation, transfer, liberation, and enchainment. This short review highlights recent approaches for the production of LCB polyolefins that can provide a roadmap crucial for researchers in academia and industry, steering their efforts toward further advancements in the production of tailored polyolefin., (© 2024 The Authors. Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

Oxabornyl polyenes represent a unique group of polyketides characterized by a central polyene core flanked by a conserved oxabornyl moiety and a structurally diverse oxygen heterocyclic ring. They are widely distributed in fungi and possess a variety of biological activities. Due to the significant spatial separation between the two stereogenic ring systems, it is difficult to establish their overall relative configurations. Here, we isolated three oxabornyl polyenes, prugosenes A1-A3 ( 1 - 3 ), from Talaromyces sp. JNU18266-01. Although these compounds were first reported from Penicillium rugulosum , their overall relative and absolute configurations remained unassigned. By employing ozonolysis in combination with ECD calculations, we were able to establish their absolute configurations, and additionally obtained seven new chemical derivatives ( 4 - 10 ). Notably, through NMR data analysis and quantum chemical calculations, we achieved the structural revision of prugosene A2. Furthermore, prugosenes A1-A3 exhibited potent antiviral activity against the respiratory syncytial virus, with compound 1 displaying an IC 50 value of 6.3 μM. Our study thus provides a valuable reference for absolute configuration assignment of oxabornyl polyene compounds.

One useful technique for increasing the efficiency of organic dye-sensitized solar cells (DSSCs) is to extend the π-conjugated bridges between the donor (D) and the acceptor (A) units. The present study used the DFT and TD-DFT techniques to investigate the effect of lengthening the polyene bridge between the donor N, N-dimethyl-anilino and the acceptor dicyanovinyl. The results of the calculated key properties were not all in line with expectations. Planar structure was associated with increasing the π-conjugation linker, implying efficient electron transfer from the donor to the acceptor. A smaller energy gap, greater oscillator strength values, and red-shifted electronic absorption were also observed when the number of polyene units was increased. However, some results indicated that the potential of the stated dyes to operate as effective dye-sensitized solar cells is limited when the polyene bridge is extended. Increasing the polyene units causes the HOMO level to rise until it exceeds the redox potential of the electrolyte, which delays regeneration and impedes the electron transport cycle from being completed. As the number of conjugated units increases, the terminal lobes of HOMO and LUMO continue to shrink, which affects the ease of intramolecular charge transfer within the dyes. Smaller polyene chain lengths yielded the most favorable results when evaluating the efficiency of electron injection and regeneration. This means that the charge transfer mechanism between the conduction band of the semiconductor and the electrolyte is not improved by extending the polyene bridge. The open circuit voltage (V OC ) was reduced from 1.23 to 0.70 V. Similarly, the excited-state duration (τ) decreased from 1.71 to 1.23 ns as the number of polyene units increased from n = 1 to n = 10. These findings are incompatible with the power conversion efficiency requirements of DSSCs. Therefore, the elongation of the polyene bridge in such D-π-A configurations rules out its application in solar cell devices.

Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO . Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10-0.83 μg/mL, and antifungal activity against Candida albicans , with an MIC value of 3.33 μg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC 50 values ranging from 2.07 to 11.50 µM.

Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model 1 . Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers 2-6 . Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification yielded a new polyene, AM-2-19, that is renal sparing in mice and primary human renal cells, potent against hundreds of pathogenic fungal strains, resistance evasive following serial passage in vitro and highly efficacious in animal models of invasive fungal infections. Thus, rational tuning of the dynamics of interactions between small molecules may lead to better treatments for fungal infections that still kill millions of people annually 7,8 and potentially other resistance-evasive antimicrobials, including those that have recently been shown to operate through supramolecular structures that target specific lipids 9 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Polyolefins are the most commercially relevant polymers by volume. A readily available feedstock and their tailor-made microstructure allow to adapt polyolefins to many fields of application. Important molecular design features of olefin copolymers are the molar mass distribution (MMD) with the corresponding average values, comonomer type, chemical composition distribution (CCD) with the corresponding average and the tacticity distribution (TD). Advanced separation techniques i.e., high-temperature gel permeation chromatography (HT-GPC) as well as its hyphenation with high-temperature high performance liquid chromatography (HT-HPLC) in the form of high-temperature two-dimensional liquid chromatography (HT 2D-LC) have been successfully applied in this work. This allowed to deeply analyze the molecular heterogeneities of complex polyolefin terpolymers consisting of ethylene, vinyl acetate and branched vinyl ester monomers. By using filter-based infrared detection, the capabilities of HT-GPC are further extended so that the distribution of methyl- and carbonyl groups could be obtained along the molar mass axis. Using porous graphitic carbon (PGC) as a stationary phase for HT-HPLC separation provided information about the CCD of these complex polyolefins from experimental data as part of the hyphenated approach of HT 2D-LC. The latter revealed the full MMD x CCD distribution function, which is the key for a comprehensive analysis of the bivariate molecular structure of the polyolefin terpolymers., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan-Hendrik Arndt reports financial support was provided by Braskem SA. Guru Geertz reports financial support was provided by Braskem SA. Robert Bruell reports financial support was provided by Braskem SA. Sampat Singh Bhati reports a relationship with Braskem Europe that includes: employment. Hadi Mohammadi, Manoela Ellwanger Cangussu has patent #WO 2021/064,474 A1 issued to Braskem SA., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Six new polyene carboxylic acids named serpentemycins E-J ( 1 - 6 ), together with three known analogs ( 7 - 9 ), were isolated from the fermentation medium of Streptomyces sp. TB060207, which was isolated from arid soil collected from Tibet, China. The structures of the new compounds were elucidated mainly on the basis of HR-ESI-MS and NMR spectroscopic analyses. The inhibitory activities of compounds 1 - 9 against NO production in LPS-activated RAW264.7 cells were evaluated. Compound 9 has an inhibition rate of 87.09% to 60.53% at concentrations ranging from 5.0 to 40.0 µM.

Mathematically describing the length-dependence of vibrational fingerprints of polyenes is challenging, yet crucial in understanding and predicting polyene-associated molecular properties of industrially-important and vital substances. To this end, we develop an analytical relationship between the wavenumbers ν∼ C=C of the Raman-active CC stretching mode in polyene sequences (CHCH)n and the polyene length (n) using classical mechanics laws. Noteworthy, this relationship is derived from Newton's equations instead of regression approximations and validated against experimental data for degraded polyvinyl chloride (PVC), t-butyl end-capped all-trans polyenes, β-carotenes, and carotenoids. Furthermore, given this fundamental tool, we carefully re-examined or validated the up-to-now applied empirical tools; we find that: (i) A phenomenological exponential regression function ν~ C=C =1461+151.2×exp-0.07808n proves fairly suitable for describing polyenes with lengths below 24 in degraded PVC. (ii) The derived analytical relationship agrees more closely with a long-established reciprocal-length regression function ν~ C=C =1459+720/n+1 for describing carotenoids. Moreover, extensive DFT calculation results on all-trans polyenes H(CHCH) n H (n = 3-30) and polyenes end-capped with terminal vinyl chloride oligomers agree with experiment for shorter polyenes and are similar, showing that complicated calculations of ν∼ C=C for infinite degraded PVC chains reduce to the calculations on finite polyene sequences. Noteworthy, unlike other polyene length-determination tools, the proposed analytical polyene length-determination based on intrinsic physical properties could well prove to be an even more versatile tool, as it comes with the added potential for determining or correcting the elasticity constants of carbon bonds in polyene chains., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Streptomyces are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may thrive on their own in the soil, or associate with other organisms, such as plants or invertebrates. Some soil-derived strains exhibit hemolytic properties when cultivated on blood agar, raising the question of whether hemolysis could be a virulence factor of the bacteria. In this work we examined hemolytic compound production in 23 β-hemolytic Streptomyces isolates; of these 12 were soil-derived, 10 were arthropod-associated, and 1 was plant-associated. An additional human-associated S. sp. TR1341 served as a control. Mass spectrometry analysis suggested synthesis of polyene molecules responsible for the hemolysis: candicidins, filipins, strevertene A, tetrafungin, and tetrin A, as well as four novel polyene compounds (denoted here as polyene A, B, C, and D) in individual liquid cultures or paired co-cultures. The non-polyene antifungal compounds actiphenol and surugamide A were also identified. The findings indicate that the ability of Streptomyces to produce cytolytic compounds (here manifested by hemolysis on blood agar) is an intrinsic feature of the bacteria in the soil environment and could even serve as a virulence factor when colonizing available host organisms. Additionally, a literature review of polyenes and non-polyene hemolytic metabolites produced by Streptomyces is presented.

Dinitrogen heterocycles are among the most important molecular structures, and the synthesis of these types of structures through intermolecular 1,2-diamination of olefins is a direct and efficient method. However, the types of nitrogen sources are mostly derived from ureas or arylamines, and nitrogen sources from aliphatic amines are still limited due to their distinct electronic and steric effects. Herein, we report a palladium-catalyzed aerobic intermolecular 1,2-diamination of conjugated dienes, using ethanediamine and α-amino amide derivatives as nitrogen sources respectively, for the synthesis of piperazines and 2-piperazinones in good yields (up to 95 %) and with high regio- and chemoselectivities., (© 2022 Wiley-VCH GmbH.)

Ambreinolide is a natural terpenoid with great value for perfume industry and natural product synthesis. Herein we report a novel total synthesis of ambreinolide on multigram-scale that employs a regio- and diastereoselective, high yielding, proton-initiated polyene cyclization using a catalyst easily generated in situ. Molecular structures were unambiguously confirmed by X-ray crystallography., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

As valuable antibiotics, microbial natural products have been in use for decades in various fields. Among them are polyene compounds including nystatin, amphotericin, and nystatin-like Pseudonocardia polyenes (NPPs). Polyene macrolides are known to possess various biological effects, such as antifungal and antiviral activities. NPP A1, which is produced by Pseudonocardia autotrophica , contains a unique disaccharide moiety in the tetraene macrolide backbone. NPP B1, with a heptane structure and improved antifungal activity, was then developed via genetic manipulation of the NPP A1 biosynthetic gene cluster (BGC). Here, we generated a Streptomyces artificial chromosomal DNA library to isolate a large-sized NPP B1 BGC. The NPP B1 BGC was successfully isolated from P. autotrophica chromosome through the construction and screening of a bacterial artificial chromosome (BAC) library, even though the isolated 140-kb BAC clone (named pNPPB1s) lacked approximately 8 kb of the right-end portion of the NPP B1 BGC. The additional introduction of the pNPPB1s as well as co-expression of the 32-kb portion including the missing 8 kb led to a 7.3-fold increase in the production level of NPP B1 in P. autotrophica . The qRT-PCR confirmed that the transcription level of NPP B1 BGC was significantly increased in the P. autotrophica strain containing two copies of the NPP B1 BGCs. Interestingly, the NPP B1 exhibited a previously unidentified SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibition activity in vitro. These results suggest that the Streptomyces BAC cloning of a large-sized, natural product BGC is a valuable approach for titer improvement and biological activity screening of natural products in actinomycetes.

Alternapyrone is a highly methylated polyene α-pyrone biosynthesised by a highly reducing polyketide synthase. Mutations of the catalytic dyad residues, H1578A/Q and E1604A, of the C -methyltransferase domain resulted in either significantly reduced or no production of alternapyrone, indicating the importance of C -methylation for alternapyrone biosynthesis.

An enantioselective Diels-Alder (DA) reaction of α-acyloxy enones has been developed to synthesize chiral oxidized cyclohexenes. Yttrium(III) triflate, in conjunction with a chiral pyridinebisimidazoline (PyBim) ligand, was found to catalyze the asymmetric [4 + 2] cycloaddition with a variety of dienes and α-acyloxy enone dienophiles. Using this method, terpinene-4-ol, a key intermediate in the synthesis of commercial herbicide cinmethylin, can be prepared in four steps from isoprene. A combination of kinetic data and NMR studies support a mechanism involving reversible binding of a dienophile to a yttrium catalyst followed by cycloaddition with a diene as the rate-determining step.

Over the past few decades (covering 1972 to 2022), astounding progress has been made in the elucidation of structures, bioactivities and biosynthesis of polyene macrolactams (PMLs), but they have only been partially summarized. PMLs possess a wide range of biological activities, particularly distinctive fungal inhibitory abilities, which render them a promising drug candidate. Moreover, the unique biosynthetic pathways including β-amino acid initiation and pericyclic reactions were presented in PMLs, leading to more attention from inside and outside the natural products community. According to current summation, in this review, the chem- and bio-diversity of PMLs from marine and terrestrial sources are considerably rich. A systematic, critical and comprehensive overview is in great need. This review described the PMLs' general structural features, production strategies, biosynthetic pathways and the mechanisms of bioactivities. The challenges and opportunities for the research of PMLs are also discussed.

We report the development of ureas as sterically undemanding pro-ligands for Pd catalysis. N -Arylureas outperform phosphine ligands for the Pd-catalyzed heteroannulation of N -tosyl- o -bromoanilines and 1,3-dienes, engaging diverse coupling partners for the preparation of 2-subsituted indolines, including sterically demanding substrates that have not previously been tolerated. Experimental and computational studies on model Pd-urea and Pd-ureate complexes are consistent with monodentate binding through the nonsubstituted nitrogen, which is uncommon for metal-ureate complexes.

The ability to selectively introduce diverse functionality onto hydrocarbons is of substantial value in the synthesis of both small molecules and polymers. Herein, we report an approach to aliphatic carbon-hydrogen bond diversification using radical chain transfer featuring an easily prepared O -alkenylhydroxamate reagent, which upon mild heating facilitates a range of challenging or previously undeveloped aliphatic carbon-hydrogen bond functionalizations of small molecules and polyolefins. This broad reaction platform enabled the functionalization of postconsumer polyolefins in infrastructure used to process plastic waste. Furthermore, the chemoselective placement of ionic functionality onto a branched polyolefin using carbon-hydrogen bond functionalization upcycled the material from a thermoplastic into a tough elastomer with the tensile properties of high-value polyolefin ionomers.

Strong interactions between the host cyclodextrin and the threading guest polymer were introduced by selective modifications to the polymer of a polybutadine-based polyrotaxane. The changes in the intercomponent interactions influenced the mobility of the threading polymer that was confined in the glassy host framework, resulting in different mechanical properties.

Chemical exploration of the recently described Australian fungus, Aspergillus burnettii , uncovered a new metabolite, burnettiene A. Here, we characterise the structure of burnettiene A as a polyene-decalin polyketide. Bioinformatic analysis of the genome of A. burnettii identified a putative biosynthetic gene cluster for burnettiene A ( bue ), consisting of eight genes and sharing similarity to the fusarielin gene cluster. Introduction of the reassembled bue gene cluster into Aspergillus nidulans for heterologous expression resulted in the production of burnettiene A under native promoters. Omission of bueE encoding a cytochrome P450 led to the production of preburnettiene A, confirming that BueE is responsible for catalysing the regiospecific multi-oxidation of terminal methyl groups to carboxylic acids. Similarly, bueF was shown to encode an ester-forming methyltransferase, with its omission resulting in the production of the tricarboxylic acid, preburnettiene B. Introduction of an additional copy of the transcription factor bueR under the regulation of the gpdA promoter significantly improved the heterologous production of the burnettienes. Burnettiene A displayed strong in vitro cytotoxicity against mouse myeloma NS-1 cells (MIC 0.8 μg mL -1 ).

A transmembrane proton gradient is generated and maintained by proton pumps in a cell. Metagenomics studies have recently identified a new category of rhodopsin intermediates between type-1 rhodopsins and heliorhodopsins, named schizorhodopsins (SzRs). SzRs are light-driven inward proton pumps. Comprehensive resonance Raman measurements were conducted to characterize the structure of the retinal chromophore in the unphotolyzed state of four SzRs. The spectra of all four SzRs show that the retinal chromophore is in the all- trans and 15- anti configuration and that the Schiff base is protonated. The polyene chain is planar in the center of the retinal chromophore and is twisted in the vicinity of the protonated Schiff base. The protonated Schiff base in the SzRs forms a stronger hydrogen bond than that in outward proton-pumping rhodopsins. We determined that the hydrogen-bonding partner of the protonated Schiff base is not a water molecule but an amino acid residue, presumably an Asp residue in helix G. The present observations provide valuable insights into the inward proton-pumping mechanism of SzRs.

Internal conversion (IC) between the two lowest singlet excited states, 1 1 B u + and 2 1 A g - , of s- trans -butadiene and s- trans -hexatriene is investigated using a series of single- and multi- reference wave function and density functional theory (DFT) methodologies. Three independent types of the equation-of-motion coupled-cluster (EOMCC) theory capable of providing an accurate and balanced description of one- as well as two-electron transitions, abbreviated as δ-CR-EOMCC(2,3), DIP-EOMCC(4h2p){ N o }, and DEA-EOMCC(4p2h){ N u } or DEA-EOMCC(3p1h,4p2h){ N u }, consistently predict that the 1 1 B u + /2 1 A g - crossing in both molecules occurs along the bond length alternation coordinate. However, the analogous 1 1 B u + and 2 1 A g - potentials obtained with some multireference approaches, such as CASSCF and MRCIS(D), as well as with the linear-response formulation of time-dependent DFT (TDDFT), do not cross. Hence, caution needs to be exercised when studying the low-lying singlet excited states of polyenes with conventional multiconfigurational methods and TDDFT. The multistate many-body perturbation theory methods, such as XMCQDPT2, do correctly reproduce the curve crossing. Among the simplest and least expensive computational methodologies, the DFT approaches that incorporate the contributions of doubly excited configurations, abbreviated as MRSF (mixed reference spin-flip) TDDFT and SSR(4,4), accurately reproduce our best EOMCC results. This is highly promising for nonadiabatic molecular dynamics simulations in larger systems.

Being a methyl ester of partricin, the mepartricin complex is the active substance of a drug called Ipertrofan (Tricandil), which was proven to be useful in treatment of benign prostatic hyperplasia and chronic nonbacterial prostatitis/chronic pelvic pain syndrome. Nevertheless, no direct structural evidence on the stereochemistry of its components has been presented to date. In this contribution, we have conducted detailed, NMR-driven stereochemical studies on mepartricins A and B, aided by molecular dynamics simulations. The absolute configuration of all the stereogenic centers of mepartricin A and B was defined as 3 R , 7 R , 9 R , 11 S , 13 S , 15 R , 17 S , 18 R , 19 S , 21 R , 36 S , 37 R , and 38 S , and proposed as 41 R . The geometry of the heptaenic chromophore of both compounds has been established as 22 E , 24 E , 26 E , 28 Z , 30 Z , 32 E , and 34 E . Our studies on mepartricin ultimately proved that partricins A and B are structurally identical to the previously described main components of the aureofacin complex: gedamycin and vacidin, respectively. The knowledge of the stereochemistry of this drug is a fundamental matter not only in terms of studies on its molecular mode of action, but also for potential derivatization, aiming at improvement of its pharmacological properties.

This paper presents the results of the first part of testing a novel electrospun fiber mat based on a unique macromolecule: polyisobutylene (PIB). A PIB-based compound containing zinc oxide (ZnO) was electrospun into self-supporting mats of 203.75 and 295.5 g/m 2 that were investigated using a variety of techniques. The results show that the hydrophobic mats are not cytotoxic, resist fibroblast cell adhesion and biofilm formation and are comfortable and easy to breathe through for use as a mask. The mats show great promise for personal protective equipment and other applications.

Aryl polyenes (APE) are one of the most widespread secondary metabolites among gram-negative bacteria. In Acinetobacter baumannii, strains belonging to the virulent global clone 2 (GC2) mostly contain APE biosynthesis genes; its relevance in elevated pathogenicity is of great interest. APE biosynthesis gene clusters harbor two ketosynthases (KSs): the heterodimeric KS-chain length factor complex, ApeO-ApeC, and the homodimeric ketoacyl-acyl carrier protein synthase I (FabB)-like KS, ApeR. The role of the two KSs in APE biosynthesis is unclear. We determined the crystal structures of the two KSs from a pathogenic A. baumannii strain. ApeO-ApeC and ApeR have similar cavity volumes; however, ApeR has a narrow cavity near the entrance. In vitro assay based on the absorption characteristics of polyene species indicated the generation of fully elongated polyene with only ApeO-ApeC, probably because of the funnel shaped active site cavity. However, adding ApeR to the reaction increases the throughput of APE biosynthesis. Mutagenesis at Tyr135 in the active site cavity of ApeR reduces the activity significantly, which suggests that the stacking of the aryl group between Tyr135 and Phe202 is important for substrate recognition. Therefore, the two KSs function complementarily in the generation of APE to enhance its production., (© 2021. The Author(s).)

In this work, the coordination-based energy sacrificial bonds have been constructed in the interphase between lignin and polyolefin elastomer to prepare high performance lignin-based thermoplastic elastomers (TPEs). The strength and toughness of lignin-based TPEs can be adjusted by choosing different nitrogen heterocyclic compounds as reactive assistants and Fe 3+ or Zn 2+ as metal coordination centers. It was demonstrated that 3-Amino-1,2,4-triazole with three nitrogen atoms in the heterocyclic ring and one nitrogen branch chain could form the most efficient coordination bond system and generate the best mechanical performance. The system with ferric iron as coordination center exhibited better enhancement effect than divalent zinc. By adjusting the nitrogen-containing reactive additives or metal salts as coordination centers, the mechanical performance of the lignin-based TPE can be regulated, which provides a method for making green bio-composites with good strength and toughness, and also promotes the high value utilization of lignin in polymer materials., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aurantinins (ARTs) are antibacterial polyketides featuring a unique 6/7/8/5-fused tetracyclic ring system and a triene side chain with a carboxyl terminus. Here we identify the art gene cluster and dissect ART's C-methyl incorporation patterns to study its biosynthesis. During this process, an apparently redundant methyltransferase Art28 was characterized as a malonyl-acyl carrier protein O-methyltransferase, which represents an unusual on-line methyl esterification initiation strategy for polyketide biosynthesis. The methyl ester bond introduced by Art28 is kept until the last step of ART biosynthesis, in which it is hydrolyzed by Art9 to convert inactive ART 9B to active ART B. The cryptic reactions catalyzed by Art28 and Art9 represent a protecting group biosynthetic logic to render the ART carboxyl terminus inert to unwanted side reactions and to protect producing organisms from toxic ART intermediates. Further analyses revealed a wide distribution of this initiation strategy for polyketide biosynthesis in various bacteria., (© 2021. The Author(s).)

New approaches are still needed to fully explore the biosynthetic potential of microbes. We recently devised a melC reporter-guided fermentation media screening approach for targeted activation of cryptic gene clusters. Using this approach, we successfully activated the expression of the hcl gene cluster in Streptomyces sp. LZ35 and discovered a novel polyene macrolide hexacosalactone A ( 1 ).

Aryl polyenes (APEs) are specialized polyunsaturated carboxylic acids that were identified in silico as the product of the most widespread family of bacterial biosynthetic gene clusters (BGCs). They are present in several Gram-negative host-associated bacteria, including multidrug-resistant human pathogens. Here, we characterize a biological function of APEs, focusing on the BGC from a uropathogenic Escherichia coli (UPEC) strain. We first perform a genetic deletion analysis to identify the essential genes required for APE biosynthesis. Next, we show that APEs function as fitness factors that increase protection from oxidative stress and contribute to biofilm formation. Together, our study highlights key steps in the APE biosynthesis pathway that can be explored as potential drug targets for complementary strategies to reduce fitness and prevent biofilm formation of multi-drug resistant pathogens.

Epo-C12 is a synthetic derivative of epolactaene, isolated from Penicillium sp. BM 1689-P. Epo-C12 induces apoptosis in human acute lymphoblastoid leukemia BALL-1 cells. In our previous studies, seven proteins that bind to Epo-C12 were identified by a combination of pull-down experiments using biotinylated Epo-C12 (Bio-Epo-C12) and mass spectrometry. In the present study, the effect of Epo-C12 on peroxiredoxin 1 (Prx 1), one of the proteins that binds to Epo-C12, was investigated. Epo-C12 inhibited Prx 1 peroxidase activity. However, it did not suppress its chaperone activity. Binding experiments between Bio-Epo-C12 and point-mutated Prx 1s suggest that Epo-C12 binds to Cys 52 and Cys 83 in Prx 1. The present study revealed that Prx 1 is one of the target proteins through which Epo-C12 exerts an apoptotic effect in BALL-1 cells., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Well-controlled ring-opening metathesis polymerization (ROMP) of δ-pinene is reported. The monomer is produced through a facile, metal-free, three-step synthesis from highly abundant and sustainable α-pinene. Using Grubbs third-generation catalyst, δ-pinene undergoes ROMP to high conversion (>95%) with molar mass up to 70 kg mol -1 and narrow dispersity (<1.2). A highly regioregular propagation mechanism was concluded by NMR spectroscopic analysis that revealed a head-to-tail (HT, >95%) microstructure and high trans content (>98%). Successful ROMP is corroborated with density functional theory calculations on δ-pinene's ring strain energy (∼35 kJ mol -1 ). Poly(δ-pinene) has a high glass transition temperature (∼104 °C) and a unique chiral microstructure bearing gem -dimethylcyclobutane rings. Controlled ROMP also allowed the synthesis of block copolymers containing segments of poly(δ-pinene) and polynorbornene which are discussed. Finally, bulk polymerization of δ-pinene is possible, indicating a greener approach to these materials, albeit with some loss of control.

Accumulation of plastic wastes and their effects on the ecosystem have triggered an alarm regarding environmental damage, which explains the massive investigations over the past few years, aiming technological alternatives for their proper destination and valorization. In this context, biological degradation emerges as a green route for plastic processing and recycling in a circular economy approach. Some of the main polymers produced worldwide are poly(ethylene terephthalate) (PET), polyethylene (PE) and polypropylene (PP), which are among the most recalcitrant materials in the environment. In comparison to other polymers, PET biodegradation has advanced dramatically in recent years concerning microbial and enzymatic mechanisms, being positioned in a higher technology readiness level (TRL). Even more challenging, polyolefins (PE and PP) biodegradation is hindered by their high recalcitrance, which is mainly related to stable carbon-carbon bonds. Potential microbial biocatalysts for this process have been evaluated, but the related mechanisms are still not fully elucidated. This review aims to discuss the latest developments on key microbial biocatalysts for degradation of these polymers, addressing biodegradation monitoring, intellectual property, and TRL analysis of the bioprocessing strategies using biodegradation performance, process time and scale as parameters for the evaluation.

Acute normovolemic hemodilution (ANH) is a potential transfusion method for platelets, as well as for red blood cells. However, previous studies have shown that whole blood storage in ANH decreases platelet aggregability by 14.7-76.3% and that this decrease is not recovered by reinfusion. We investigated whether a new whole blood storage method for 6 h using a polyolefin bag, based on the platelet concentrates storage method, would maintain platelet function better than the conventional method using a polyvinyl chloride bag. We demonstrated that storage of whole blood in a polyolefin bag maintained ADP-induced aggregation rates at more than twofold higher than those in a polyvinyl chloride bag, and also significantly suppressed P-selectin expression, a platelet activation marker (ADP-induced aggregation rates: 24.6 ± 5.1% vs. 51.7 ± 11.5%, p = 0.002; P-selectin expression; 50.3 ± 8.4MFI vs. 31.6 ± 9.3MFI, p = 0.018). These results could be attributed to the high gas permeability of polyolefin, which lowered PCO 2 and maintained a high pH with or without agitation. There were no significant changes in platelet count and red blood cell parameters due to the storage methods. Our results suggest that ANH using polyolefin bags is advantageous in improving hemostatic function compared to the conventional method.

Artificial muscle materials promise incredible applications in actuators, robotics and medical apparatus, yet the ability to mimic the full characteristics of skeletal muscles into synthetic materials remains a huge challenge. Herein, inspired by the dynamic sacrificial bonds in biomaterials and the self-strengthening of skeletal muscles by physical exercise, high performance artificial muscle material is prepared by rearrangement of sacrificial coordination bonds in the polyolefin elastomer via a repetitive mechanical training process. Biomass lignin is incorporated as a green reinforcer for the construction of interfacial coordination bonds. The prepared artificial muscle material exhibits high actuation strain (>40%), high actuation stress (1.5 MPa) which can lift more than 10,000 times its own weight with 30% strain, characteristics of excellent self-strengthening by mechanical training, strain-adaptive stiffening, and heat/electric programmable actuation performance. In this work, we show a facile strategy for the fabrication of intelligent materials using easily available raw materials.

Successfully interfacing enzymes and biomachinery with polymers affords on-demand modification and/or programmable degradation during the manufacture, utilization and disposal of plastics, but requires controlled biocatalysis in solid matrices with macromolecular substrates 1-7 . Embedding enzyme microparticles speeds up polyester degradation, but compromises host properties and unintentionally accelerates the formation of microplastics with partial polymer degradation 6,8,9 . Here we show that by nanoscopically dispersing enzymes with deep active sites, semi-crystalline polyesters can be degraded primarily via chain-end-mediated processive depolymerization with programmable latency and material integrity, akin to polyadenylation-induced messenger RNA decay 10 . It is also feasible to achieve processivity with enzymes that have surface-exposed active sites by engineering enzyme-protectant-polymer complexes. Poly(caprolactone) and poly(lactic acid) containing less than 2 weight per cent enzymes are depolymerized in days, with up to 98 per cent polymer-to-small-molecule conversion in standard soil composts and household tap water, completely eliminating current needs to separate and landfill their products in compost facilities. Furthermore, oxidases embedded in polyolefins retain their activities. However, hydrocarbon polymers do not closely associate with enzymes, as their polyester counterparts do, and the reactive radicals that are generated cannot chemically modify the macromolecular host. This study provides molecular guidance towards enzyme-polymer pairing and the selection of enzyme protectants to modulate substrate selectivity and optimize biocatalytic pathways. The results also highlight the need for in-depth research in solid-state enzymology, especially in multi-step enzymatic cascades, to tackle chemically dormant substrates without creating secondary environmental contamination and/or biosafety concerns.

Objectives: The co-encapsulation of bioactive peptides obtained from degradation of chicken feathers and flexirubin-type pigment produced by Chryseobacterium sp. kr6 into phosphatidylcholine liposomes was investigated., Results: Control empty liposomes showed mean diameter of 168.5 nm, varying to 185.4, 102.0 and 98.5 nm after the encapsulation of peptides, pigment and their co-encapsulation, respectively. Control liposomes presented zeta potential of - 20.9 mV, while the formulations containing the bioactive compounds showed values of - 30 mV or higher in magnitude. Infrared analysis revealed typical spectra for phosphatidylcholine, suggesting that no new chemical bonds were formed after encapsulation. ABTS radical scavenging assay showed that the antioxidant activity of the compounds was maintained after encapsulation., Conclusions: Feather waste can be a valuable substrate for simultaneous production of antioxidant peptides and pigment by Chryseobacterium sp. kr6, and their encapsulation into liposomes may be a suitable alternative for delivery of these natural antioxidants.

T-cell acute lymphoblastic leukemia (T-ALL) is a hardly curable disease with a high relapse rate. 20 analogs were synthesized based on the structures of two kinds of fungi-derived polyenylpyrrole products (rumbrin (1) and auxarconjugatin-B (2)) to suppress the growth of T-ALL-derived cell line CCRF-CEM and tested for growth-inhibiting activity. The octatetraenylpyrrole analog gave an IC 50 of 0.27 μM in CCRF-CEM cells, while it did not affect Burkitt lymphoma-derived cell line Raji and the cervical cancer cell line HeLa, or the oral cancer cell line HSC-3 (IC 50  > 10 μM). This compound will be a promising compound for developing T-ALL-specific drugs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Two types of nanocomposite films, polyethylene/silver (PE/Ag) and polypropylene/silver (PP/Ag), were prepared and characterised. Assessment of silver released under the effect of ionising irradiation was performed on the nanocomposite films. The release experiment was carried out by immersing the nanocomposite films in water, 3% acetic acid or 95% ethanol as food simulants and measuring the Ag release from nanocomposite films treated with and without gamma or electron beam irradiation at a dose of 10 kGy. In general, irradiation treatment increased the Ag release regardless of the type of polymer and food simulant. One reason could be radiation-induced metal oxidation at the surface which in turn promoted ion release into food simulants. The oxidising radicals produced by radiation in solution could be another factor speeding up metal oxidation and subsequent ion release. When comparisons were made between the two types of irradiation, greater Ag release into water and 3% acetic acid was observed after electron beam irradiation, while gamma irradiation was likely to induce greater Ag release into 95% ethanol. Such phenomena reveal the influence of different types of radiation on the solutions which in turn affect the Ag release.

In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of complex molecules is the Diels-Alder cycloaddition. This reaction is between a diene and a dienophile. Among the most important dienes are the cyclic dienes, as they facilitate the reaction. This review considers the synthesis and reactivity of one of these dienes with special characteristics-it is cyclic and has an electron withdrawing group. This building block has been used for the synthesis of biologically active compounds and is present in natural compounds with interesting properties.

Hitachimycin is a macrolactam antibiotic with an ( S )-β-phenylalanine (β-Phe) at the starter position of its polyketide skeleton. ( S )-β-Phe is formed from l-α-phenylalanine by the phenylananine-2,3-aminomutase HitA in the hitachimycin biosynthetic pathway. In this study, we produced new hitachimycin analogs via mutasynthesis by feeding various ( S )-β-Phe analogs to a Δ hitA strain. We obtained six hitachimycin analogs with F at the ortho , meta , or para position and Cl, Br, or a CH 3 group at the meta position of the phenyl moiety, as well as two hitachimycin analogs with thienyl substitutions. Furthermore, we carried out a biochemical and structural analysis of HitB, a β-amino acid-selective adenylation enzyme that introduces ( S )-β-Phe into the hitachimycin biosynthetic pathway. The K M values of the incorporated ( S )-β-Phe analogs and natural ( S )-β-Phe were similar. However, the K M values of unincorporated ( S )-β-Phe analogs with Br and a CH 3 group at the ortho or para position of the phenyl moiety were high, indicating that HitB functions as a gatekeeper to select macrolactam starter units during mutasynthesis. The crystal structure of HitB in complex with ( S )-β-3-Br-phenylalanine sulfamoyladenosine (β- m -Br-Phe-SA) revealed that the bulky meta- Br group is accommodated by the conformational flexibility around Phe328, whose side chain is close to the meta position. The aromatic group of β- m -Br-Phe-SA is surrounded by hydrophobic and aromatic residues, which appears to confer the conformational flexibility that enables HitB to accommodate the meta -substituted ( S )-β-Phe. The new hitachimycin analogs exhibited different levels of biological activity in HeLa cells and multidrug-sensitive budding yeast, suggesting that they may target different molecules.