共检索到187条,权限内显示50条;
[学术文献 ] Mechanistic investigation of repurposed photoenzymes with new-to-nature reactivity 进入全文
Current Opinion in Green and Sustainable Chemistry
Biocatalysis is widely renowned for its remarkable efficiency, selectivity, and known for operating under mild conditions. While most enzymatic reactions progress without light irradiation, recent studies have identified light as a crucial factor in the activation of certain naturally occurring enzymes. These findings have spurred the rapid advancement of photoenzymatic catalysis in the past few years, where enzymes are not typically known for light activation perform excited-state chemistry with or without the presence of external photocatalysts to facilitate new-to-nature transformations that are challenging for traditional chemical synthesis. In this review, we summarize the experimental and computational methods used to investigate the catalytic mechanisms of repurposed photoenzymes with new-to-nature reactivity and discuss how these insights can inform the design of new photoenzymatic catalytic systems.
[政策法规 ] 합성생물학 육성법 세계 최초로 제정 进入全文
朝鲜日报
韩国于2025年4月2日颁布了《合成生物学促进法》，成为全球首个制定此类法律的国家。这一法律的实施标志着韩国将合成生物学定位为国家核心技术，并致力于推动其发展。合成生物学是一门通过工程学方法设计、制造和利用生命体组成要素和系统的学科，其应用广泛，例如新冠疫苗的快速开发以及胰岛素的大规模生产，都得益于合成生物学技术。韩国在该领域的竞争力目前位居世界第7位，政府希望通过法律的实施进一步提升技术水平，确保在全球技术竞争中不落后。 根据法律，韩国科学技术信息通信部需每五年制定一次合成生物学发展基本计划，并为指定政策专业机构和研发重点机构提供依据。此外，法律的实施将加速合成生物学核心基础设施——公共“生物铸造厂”的建设。生物铸造厂利用人工智能等技术，通过快速循环工艺实现合成生物学所需的复杂过程，类似于半导体代工生产，能够快速制造生命体的组成部分。该项目已于去年通过初步可行性研究，预计规模约为1263亿韩元。 韩国科学技术信息通信部部长表示，该法律为合成生物学领域赋予了国家发展方向和战略，是重要的里程碑。韩国希望通过集中支持合成生物学的研究与开发，改变全球生物市场的格局，确保在技术霸权竞争中保持领先地位。
[学术文献 ] Biosynthesis of poly(ester amide)s in engineered Escherichia coli 进入全文
Nature Chemical Biology
The development of biobased polymers to substitute their current petroleum-based counterparts is crucial for fostering a sustainable plastic industry. Here we report the biosynthesis and characterization of a group of biopolymers, poly(ester amide)s (PEAs), in Escherichia coli. PEAs are biosynthesized by constructing a new-to-nature amino acid polymerization pathway, comprising amino acid activation by β-alanine CoA transferase and subsequent polymerization of amino acyl-CoA by polyhydroxyalkanoate synthase. The engineered E. coli strains harboring this pathway are capable of biosynthesizing various PEAs, each incorporating different amino acid monomers in varying fractions. Examination of the physical, thermal and mechanical properties reveals a dependence of molecular weight on the type of polyhydroxyalkanoate synthase, a decrease in melting temperature and crystallinity as the 3-aminopropionate monomer fraction increases and enhanced elongation at break compared to its polyester analog. The engineered bacterial system will prove beneficial for the biobased production of various PEAs using renewable resources.
[学术文献 ] Enhanced activity and self-regeneration in dynameric cross-linked enzyme nanoaggregates 进入全文
SCIENCE ADVANCES
Directed evolution, enzyme design, and effective immobilization have been used to improve the catalytic activity. Dynamic polymers offer a promising platform to improve enzyme activity in aqueous solutions. Here, amphiphilic dynamers and lipase self-assemble into nanoparticles of 150- to 600-nanometer diameter, showing remarkable threefold enhancement in catalytic activity. In addition, they also demonstrated the ability to promote the reversible refolding of the partially or completely denatured lipase. The catalytic efficiency is completed with its more convenient handling of dynameric nanoparticles facilitating the efficient recovery and reuse of the enzyme with cost-effective uses. Molecular simulation studies revealed an in-depth understanding of how the dynamer action mechanism affects the conformational changes of lipase. The dynamer served as an effective hydrophobic support, facilitating the lid opening and substrate access to the catalytic triad, resulting in a substantial activation with an improved stability and recyclability of the lipase.
[学术文献 ] Comparing and Combining Alternative Strategies for Enhancing Cytochrome P450 Peroxygenase Activity 进入全文
ACS Catalysis
Cytochrome P450 monooxygenase (CYP) enzymes have advantageous properties over chemical catalysts. However, it is often not feasible to use CYPs in larger-scale synthesis as they require additional cofactors (NAD(P)H) and electron transfer proteins. This could be overcome by transforming CYPs into peroxygenases that use H2O2. Recently, multiple strategies have been reported for converting CYPs into peroxygenases. Mutating the residues of the acid–alcohol pair in the oxygen-binding groove to those found in natural peroxygenases can promote the desired H2O2-driven activity. Another strategy is to enlarge the enzyme’s solvent channels to allow H2O2 easier access into the active site, to enhance peroxygenase activity. Here, we evaluate these different strategies by comparing the peroxygenase activities of the double I-helix mutant D251Q/T252E (the QE mutant) and the F182A mutant of the bacterial enzyme CYP199A4. We also assess whether the peroxygenase activity can be further improved by combining these mutations (to give the F182AQE mutant). The F182A mutant exhibited the highest activity toward a selection of smaller substrates that undergo O-demethylation, S-oxidation, and epoxidation reactions. All the mutants converted 4-vinylbenzoic acid into the (S)-epoxide, with the F182A mutant having the highest stereoselectivity (>99% ee). The F182A mutant was unable to oxidize 4-t-butylbenzoic acid, while the F182AQE mutant could with high activity. The F182A mutation was found to substantially alter the selectivity of the reaction with 4-ethylbenzoic acid, increasing hydroxylation activity over desaturation. The F182A mutant catalyzed significant further oxidation reactions of the primary metabolites before all the substrate had been consumed, demonstrating a relaxed substrate specificity. X-ray crystal structures of the F182A and F182AQE mutants with the substrates revealed changes in substrate binding and solvent access providing insights into these experimental observations.
[学术文献 ] Production of a δ-Lactam from Glucose through Integrating Biological and Chemical Catalysis 进入全文
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
We present a new strategy for the production of a δ-lactam from glucose that integrates biological production of triacetic acid lactone (TAL, 4-hydroxy-6-methyl-2H-2-one) with catalytic transformation of TAL into 6-methylpiperidin-2-one (MPO) through metabolic engineering, isomerization, amination, and catalytic hydrogenation/hydrogenolysis. We developed a sustainable and antibiotic-free fed-batch fermentation using genetically modified Rhodotorula toruloides IFO0880. This process achieved a yield of 2-hydroxy-6-methyl-4H-pyran-4-one (2H4P) at 0.05 g/g of glucose, corresponding to a 9.9 g/L titer. By adjusting the pH of the fermentation broth to 2, 2H4P was quantitatively converted into TAL. The TAL in the fermentation broth was directly converted by aminolysis into 4-hydroxy-6-methylpyridin-2(1H)-one (HMPO), which achieved an 18.5% yield with 94.3% purity. The HMPO yield was lower in the fermentation broth than in a clean feedstock (32.2%), suggesting that the biological impurities are inhibitors in this reaction. Further investigation revealed that lower pH levels and reduced TAL concentrations in the fermentation broth significantly decreased HMPO yields. Subsequently, the precipitated HMPO was filtered and dried and then subjected to the final catalytic conversion in H2O solvent, achieving a MPO yield of 91.8%. This integrated approach demonstrated the direct use of TAL in the filtered aqueous fermentation broth without the need to isolate TAL.
