Article
Chemistry, Multidisciplinary
Anja Greule, Thierry Izore, Daniel Machell, Mathias H. Hansen, Melanie Schoppet, James J. De Voss, Louise K. Charkoudian, Ralf B. Schittenhelm, Jeffrey R. Harmer, Max J. Cryle
Summary: Cytochrome P450 enzymes are enzymes that can perform oxidative reactions using heme. However, some of these enzymes can be damaged by oxidation, leading to decreased enzyme activity. Research has shown that the heme orientation in the active site of certain cytochrome P450 enzymes may contribute to this oxidative damage.
FRONTIERS IN CHEMISTRY
(2022)
Article
Plant Sciences
Xuan Feng, Qingzhi Zhang, David J. Clarke, Hai Deng, David O'Hagan
Summary: 3'-O-ss-Glucosyl-4',5'-didehydro-5'-deoxyadenosine 13 is a natural product of Streptomyces calvus and Streptomyces virens, and can also be generated in vitro by the enzyme NucGT. Experimental results using oxygen-18 and deuterium isotopes confirm that 13 is not a biosynthetic precursor to nucleocidin 1.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Multidisciplinary Sciences
Jin-Mei Zhang, Xuan Liu, Qian Wei, Chuanteng Ma, Dehai Li, Yi Zou
Summary: This study reconstitutes the core backbone of the cytochalasin family and describes an oxidase that catalyzes an unusual double-bond isomerization reaction. The results suggest a previously unknown function of berberine bridge enzyme-like enzymes in regulating the synthesis pathway of cytochalasan compounds.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Milda Kaniusaite, Julien Tailhades, Tiia Kittila, Christopher D. Fage, Robert J. A. Goode, Ralf B. Schittenhelm, Max J. Cryle
Summary: The biosynthesis of glycopeptide antibiotics demonstrates the exceptional ability of nonribosomal peptide synthesis to generate diverse and complex structures. An important study on the NRPS assembly lines involved in synthesizing GPAs revealed that they function as dynamic peptide assembly lines, allowing for flexible control over amino acid modifications and peptide formation, which is beneficial for the redesign of important biosynthetic systems.
Article
Biochemistry & Molecular Biology
Krishna Somaletha Chandran, John Humphries, Jason Q. D. Goodger, Ian E. Woodrow
Summary: This study identified and characterized a methyltransferase called EnOMT1 in Eucalyptus, which is responsible for the regiospecific methylation of pinostrobin, a flavanone compound. This research adds to our understanding of flavanone biosynthesis in plants and sheds light on the mechanism of chemical ornamentation in Eucalyptus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Yongyong Zhang, Mohsin T. Cheema, Larissa Ponomareva, Qing Ye, Tao Liu, Imran Sajid, Juergen Rohr, Qing-Bai She, S. Randal Voss, Jon S. Thorson, Khaled A. Shaaban
Summary: Seven new anthraquinone-derived metabolites, himalaquinones A-G, were isolated from Streptomyces sp. PU-MM59 in the Himalayas. Comparative bioactivity assessment revealed that cytotoxic landomycin and saquayamycin analogues inhibit 4E-BP1 phosphorylation and regeneration, while himalaquinone G, a new 5,6-dihydrodiol-bearing angucyclinone, also shows cytotoxic and regeneration inhibitory effects but does not affect 4E-BP1 phosphorylation. This suggests a unique mechanism for himalaquinone G and similar compounds.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Multidisciplinary
Eveline Vriens, Dries De Ruysscher, Angus N. M. Weir, Sofie Dekimpe, Gert Steurs, Ahmed Shemy, Leentje Persoons, Ana Rita Santos, Christopher Williams, Dirk Daelemans, Matthew P. Crump, Arnout Voet, Wim De Borggraeve, Eveline Lescrinier, Joleen Masschelein
Summary: In this study, the oximidine gene cluster was identified in Pseudomonas baetica, and four novel oximidine variants were characterized, including a structurally simpler intermediate. Through a combination of in vivo, in vitro, and computational approaches, the biosynthetic pathway of oximidine and an unprecedented mechanism for O-methyloxime formation were experimentally elucidated, expanding the catalytic capabilities of trans-AT PKSs and identifying potential strategies for the production of novel oximidine analogues.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Koichi Mitsudo, Yasuyuki Okumura, Kotaro Yohena, Yuji Kurimoto, Eisuke Sato, Seiji Suga
Summary: Electrochemical dehydrogenative C-O bond formation was achieved for the synthesis of sultones. In the presence of K2CO3 and H2O, constant current electrolysis of [1,1'-biphenyl]-2-sulfonyl chloride resulted in quantitative formation of aryl-fused sultone. Control experiments suggest that electrochemical oxidation of sulfonates generates sulfo radical intermediates.
Article
Plant Sciences
Shun Tamaki, Kazunari Ozasa, Toshihisa Nomura, Marumi Ishikawa, Koji Yamada, Kengo Suzuki, Keiichi Mochida
Summary: Zeaxanthin is required for the formation of functional photoreactive organelles in Euglena gracilis, highlighting the evolutionary differences between euglenophytes and chlorophytes in the photosensing mechanism. The study demonstrates the metabolic regulation of photoreactive organelle formation in Euglena gracilis and its importance in eyespot formation.
Article
Chemistry, Multidisciplinary
Yu Meng Yang, Er Juan Zhao, Wanqing Wei, Zi Fei Xu, Jing Shi, Xuan Wu, Bo Zhang, Yasuhiro Igarashi, Rui Hua Jiao, Yong Liang, Ren Xiang Tan, Hui Ming Ge
Summary: In this study, a cytochrome P450 enzyme that can catalyze the formation of a benzene ring from an acyclic polyene substrate has been characterized. Through genome mining guided by this P450 enzyme, 12 homologous type I polyketide synthase gene clusters were obtained, among which two clusters were found to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to explore the possible mechanism for the P450-catalyzed benzene ring formation, expanding our knowledge of the catalytic diversity of cytochrome P450.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Medicine, Research & Experimental
Hong Wang, Haizhou Wang, Xueyan Li, Wen Xu
Summary: This study reveals a novel molecular mechanism underlying MuRF-1-mediated internal laryngeal muscle denervated atrophy, in which MuRF-1 promotes the disequilibrium of the G/F-actin ratio by regulating G-actin ubiquitination.
Article
Biochemistry & Molecular Biology
Jiawei Zhou, Tianyuan Hu, Yuan Liu, Lichan Tu, Yadi Song, Yun Lu, Yifeng Zhang, Yuru Tong, Yujun Zhao, Ping Su, Xiaoyi Wu, Luqi Huang, Wei Gao
Summary: A cytochrome P450 monooxygenase TwCYP712K1 from Tripterygium wilfordii was found to catalyze the oxidation of friedelin to polpunonic acid in the celastrol biosynthesis pathway, as well as oxidize beta-amyrin or alpha-amyrin. The role of TwCYP712K1 in celastrol biosynthesis was further confirmed through RNA interference, and key residues of TwCYP712K1 were identified through molecular docking and site-directed mutagenesis. These findings provide a solid foundation for studying the biosynthesis of celastrol and related triterpenoids.
Article
Engineering, Environmental
Jinge Du, Na Zhang, Shuanglong Ma, Guansong Wang, Chang Ma, Guangyong Liu, Yan Wang, Jingzhen Wang, Tianjun Ni, Zhen An, Weidong Wu
Summary: C and O dual-doped g-C3N4 photocatalyst was used to activate peroxydisulfate and effectively disinfect tetracycline-resistant Escherichia coli. The study also found that the photocatalyst could degrade antibiotic resistance genes by generating more free radicals and causing oxidative stress in cells. This research provides valuable insights into the inactivation of antibiotic resistant bacteria and offers a potential strategy for preventing the dissemination of antibiotic resistance genes in water contamination.
JOURNAL OF HAZARDOUS MATERIALS
(2024)
Article
Engineering, Environmental
Jian Chen, Xiangyang Fu, Huan Chen, Zhe Wang
Summary: A Gd2O3-cluster decorated O-doping g-C3N4 photocatalyst with enhanced visible-light photocatalytic activity was prepared using an ethanol assisted solvothermalpolycondensation method. The photocatalyst showed superior performance, reusability and impressive TOC removal of about 60%. The improved photocatalytic activity was attributed to oxygen doping and Gd2O3 decoration.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Microbiology
Soma Mandal, Tanya Parish
Summary: The benzoxaborole series has shown antimicrobial activity against Escherichia coli, with resistant mutants showing mutations in the enoyl acyl carrier protein FabI. The physical interaction between benzoxaborole and FabI is dependent on the cofactor NAD(+), providing further scope for development against Gram-negative pathogens.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Paul R. F. Cordero, Rhys Grinter, Kiel Hards, Max J. Cryle, Coral G. Warr, Gregory M. Cook, Chris Greening
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Review
Biochemistry & Molecular Biology
Edward Marschall, Max J. Cryle, Julien Tailhades
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Chemistry, Organic
Yongwei Zhao, Robert J. A. Goode, Ralf B. Schittenhelm, Julien Tailhades, Max J. Cryle
JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Milda Kaniusaite, Julien Tailhades, Tiia Kittila, Christopher D. Fage, Robert J. A. Goode, Ralf B. Schittenhelm, Max J. Cryle
Summary: The biosynthesis of glycopeptide antibiotics demonstrates the exceptional ability of nonribosomal peptide synthesis to generate diverse and complex structures. An important study on the NRPS assembly lines involved in synthesizing GPAs revealed that they function as dynamic peptide assembly lines, allowing for flexible control over amino acid modifications and peptide formation, which is beneficial for the redesign of important biosynthetic systems.
Article
Microbiology
Rhys Grinter, Blair Ney, Rajini Brammananth, Christopher K. Barlow, Paul R. F. Cordero, David L. Gillett, Thierry Izore, Max J. Cryle, Liam K. Harold, Gregory M. Cook, George Taiaroa, Deborah A. Williamson, Andrew C. Warden, John G. Oakeshott, Matthew C. Taylor, Paul K. Crellin, Colin J. Jackson, Ralf B. Schittenhelm, Ross L. Coppel, Chris Greening
Review
Biochemistry & Molecular Biology
Yongwei Zhao, Y. T. Candace Ho, Julien Tailhades, Max Cryle
Summary: Researchers are intrigued by the complex biosynthesis of glycopeptide antibiotics, particularly the role of the X-domain in recruiting P450 enzymes. In vitro studies have provided insights into the tolerances and limitations of the GPA cyclisation cascade, paving the way for future reengineering of this important antibiotic class.
Article
Biochemistry & Molecular Biology
Milda Kaniusaite, Tiia Kittila, Robert J. A. Goode, Ralf B. Schittenhelm, Max J. Cryle
ACS CHEMICAL BIOLOGY
(2020)
Letter
Biochemistry & Molecular Biology
Daniel L. Machell, Mathias H. Hansen, Max J. Cryle
Summary: Detection of pyrophosphate is crucial for quantifying enzyme activity, especially adenylation domain activity in non-ribosomal peptide synthesis. After screening, viable replacement enzymes with higher activity have been identified, allowing the continued use of the established online assay for pyrophosphate detection.
Article
Biochemistry & Molecular Biology
Y. T. Candace Ho, Ralf B. Schittenhelm, Dumitrita Iftime, Evi Stegmann, Julien Tailhades, Max J. Cryle
Summary: Glycopeptide antibiotics inhibit bacterial cell-wall biosynthesis by sequestration of precursor lipid II. The oxidative crosslinking of the core peptide during GPA biosynthesis is essential and challenging. Understanding the activity and selectivity of Oxy enzymes is important for future engineering of this compound class.
Article
Chemistry, Multidisciplinary
Rania A. A. Hashad, Edwina Jap, Joanne L. L. Casey, Y. T. Candace Ho, Alexander Wright, Claudia Thalmann, Mark Sleeman, David W. W. Lupton, Christoph E. E. Hagemeyer, Max J. J. Cryle, Remy Robert, Karen Alt
Summary: A highly effective 2-step system using engineered methionine residues was used for site-specific antibody modification and conjugation. This system offers a novel way to fundamentally change the process of antibody bioconjugation. The versatility of this system was demonstrated by incorporating a fluorescent dye and can be applied to a wide variety of conjugation partners.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Songya Zhang, Yunliang Chen, Jing Zhu, Qiujie Lu, Max J. Cryle, Youming Zhang, Fu Yan
Summary: Streptomyces bacteria are widely distributed in terrestrial and marine environments and are a rich source of active natural products due to their metabolic diversity. This review highlights the importance of nonribosomal lipopeptides as important natural products with diverse biological activities that play crucial roles in the lifestyle of Streptomyces. Recent advances in the biosynthesis of lipopeptide antibiotics produced by Streptomyces have greatly contributed to our understanding of their structures, properties, biosynthetic mechanisms, chemical and chemoenzymatic synthesis, and biological functions. The use of genome mining techniques has led to the discovery of many novel lipopeptides, further demonstrating their potential for future development in modern medicine.
NATURAL PRODUCT REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Y. T. Candace Ho, Joe A. Kaczmarski, Julien Tailhades, Thierry Izore, David L. Steer, Ralf B. Schittenhelm, Manuela Tosin, Colin J. Jackson, Max J. Cryle
Summary: Nonribosomal peptide synthetases play a significant role in producing essential peptide natural products, with carrier proteins as their core component. By replacing the CP substrate thioesters with stabilized ester analogues, active condensation domain complexes are formed, while amide stabilization leads to non-functional complexes.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Jennifer A. E. Payne, Ketav Kulkarni, Thierry Izore, Alex J. Fulcher, Anton Y. Peleg, Marie-Isabel Aguilar, Max J. Cryle, Mark P. Del Borgo
Summary: A new antimicrobial material was designed, synthesised and characterised by the self-assembly of two distinct beta-peptide monomers, which showed inhibitory effects on drug-resistant bacteria like MRSA. This study provides insights into the design of peptide-based supramolecular assemblies with antibacterial activity.
NANOSCALE ADVANCES
(2021)
Article
Chemistry, Multidisciplinary
Daniel J. Leng, Anja Greule, Max J. Cryle, Manuela Tosin
Summary: Chemical probes were used to capture biosynthetic intermediates generated in the nonribosomal peptide formation of vancomycin in vivo. The putative intercepted intermediates were characterised via HR-LC-MS2, providing insights into the timing of the first chlorination of the peptide backbone by the halogenase VhaA. This information is significant for enzyme engineering towards the production of novel glycopeptides.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Milda Kaniusaite, Robert J. A. Goode, Julien Tailhades, Ralf B. Schittenhelm, Max J. Cryle