Article
Chemistry, Multidisciplinary
Munro Passmore, Angelo Gallo, Jozef R. Lewandowski, Matthew Jenner
Summary: This study reveals specific interactions between ACP and KR domains from trans-AT PKSs, indicating highly optimized interaction interfaces driven by evolutionary processes. The results provide valuable rules for future engineering efforts of biosynthetic assembly lines.
Article
Chemistry, Multidisciplinary
Xiaolin Zou, Zhen Hui, Robert A. Shepherd, Shuaiqiang Zhao, Yanfei Wu, Zhuanglin Shen, Cuiping Pang, Shipeng Zhou, Zehai Yu, Jiahai Zhou, Bradly S. Moore, Laura M. Sanchez, Xiaoyu Tang
Summary: This study provides a comprehensive exploration of the genetic and biochemical aspects of the enzymes responsible for the assembly and cleavage of the acylated peptide prodrug scaffolds in the assembly line biosynthesis of didemnin cyclic peptides. The findings shed light on the complex prodrug release mechanism underlying the synthesis and secretion of didemnin compounds and offer novel insights into the expanded role of CAAX hydrolases in microbes. This knowledge can be used for the strategic design of genome mining approaches to discover new bioactive natural products that employ similar prodrug biochemical strategies.
Article
Multidisciplinary Sciences
Vitor Mendes, Simon R. Green, Joanna C. Evans, Jeannine Hess, Michal Blaszczyk, Christina Spry, Owain Bryant, James Cory-Wright, Daniel S-H Chan, Pedro H. M. Torres, Zhe Wang, Navid Nahiyaan, Sandra O'Neill, Sebastian Damerow, John Post, Tracy Bayliss, Sasha L. Lynch, Anthony G. Coyne, Peter C. Ray, Chris Abell, Kyu Y. Rhee, Helena I. M. Boshoff, Clifton E. Barry, Valerie Mizrahi, Paul G. Wyatt, Tom L. Blundell
Summary: Coenzyme A (CoA) is a crucial factor in various metabolic pathways and cellular processes, particularly in prokaryotes such as Mycobacterium tuberculosis. The biosynthesis of CoA involves five steps, with the second and third steps catalyzed by a bifunctional protein CoaBC in most prokaryotes. The researchers identified inhibitors of M. tuberculosis CoaB through a high-throughput screen and discovered a cryptic allosteric binding site within the enzyme.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Mengmeng Zheng, Jun Zhang, Wan Zhang, Lu Yang, Xiaoli Yan, Wenya Tian, Zhihao Liu, Zhi Lin, Zixin Deng, Xudong Qu
Summary: In this study, an ACS enzyme was improved through protein engineering, leading to enhanced activity in synthesizing acyl-CoAs. By combining it with carboxylases, several novel antimycin analogues were successfully produced through a modified biosynthetic pathway. This study expands the catalytic mode of ACSs and provides an important tool for the biosynthesis of acyl-CoA-derived natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Hua-Qi Wang, Shu-Bin Mou, Wen Xiao, Huan Zhou, Xu-Dong Hou, Su-Jing Wang, Qian Wang, Jiali Gao, Zhiyi Wei, Lijun Liu, Zheng Xiang
Summary: CylK is a key enzyme that catalyzes the formation of the cylindrocyclophane scaffold through Friedel-Crafts alkylation reactions, exhibiting regioselectivity and stereospecificity. This study proposes a concerted double-activation mechanism to explain the enzymatic alkylation with regioselectivity and stereospecificity, based on crystal structures, free energy simulations, and site-directed mutagenesis experiments.
Article
Plant Sciences
Christina Rabeler, Mingjie Chen, Nick Kaplinsky
Summary: Phospholipid biosynthesis is a crucial metabolic pathway that affects plant growth and development. Choline/ethanolamine kinases (CEKs) are enzymes responsible for the synthesis of polar head groups on plant phospholipids. Through the study of a CEK4 mutant called bst, new roles for CEK4 in plant development and response to the environment have been revealed.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Yu Shi, Ning Zang, Ningjie Lou, Yongchang Xu, Jingdu Sun, Man Huang, Huimin Zhang, Huijie Lu, Chun Zhou, Youjun Feng
Summary: This study systematically describes the Fak system of the zoonotic pathogen Streptococcus suis and reveals the mechanism of FakA working with FakB partners in host fatty acid scavenging through crystal structure determination and in vitro experiments.
Article
Chemistry, Multidisciplinary
Hanna Chen, Lin Zhong, Haibo Zhou, Tao Sun, Guannan Zhong, Qiang Tu, Yan Zhuang, Xianping Bai, Xingyan Wang, Jiaying Xu, Liqiu Xia, Yuemao Shen, Youming Zhang, Xiaoying Bian
Summary: Nonribosomal peptide synthetases (NRPSs) can incorporate nonproteinogenic amino acids into peptidyl backbones to increase structural diversity. This study identified a class of linear lipoheptapeptides featuring two unusual residues and revealed the β-hydroxylation mechanisms of Asp and His, which require the concerted action of specific enzymes and domains.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Katherine D. Bauman, Vikram V. Shende, Percival Yang-Ting Chen, Daniela B. B. Trivella, Tobias A. M. Gulder, Sreekumar Vellalath, Daniel Romo, Bradley S. Moore
Summary: This study reports an enzymatic route to the salinosporamide core and reveals the catalytic role of a ketosynthase, SalC, in transacylation and bond-forming reactions. The crystal structure of SalC and site-directed mutagenesis studies proposed a bicyclization reaction mechanism. This work challenges our understanding of ketosynthase enzymes and provides a foundation for the streamlined production of clinically relevant chemotherapeutics in the future.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Plant Sciences
Xiaomin Hu, Yuanyuan Shi, Bingya Jiang, Jie Fu, Xingxing Li, Shufen Li, Guizhi Sun, Weicong Ren, Xinxin Hu, Xuefu You, Zhiyong Liu, Xingli Han, Tianyu Zhang, Bin Hong, Linzhuan Wu
Summary: A new congener of chuangxinmycin, 3-methylchuangxinmycin, was identified and its structure was determined. The vitamin B12-dependent radical SAM enzyme CxnA/A1 was found to be responsible for the methylation of 3-demethylchuangxinmycin in the biosynthesis of chuangxinmycin, indicating its potential for iterative methylation for the production of 3-methylchuangxinmycin. In vitro assays showed significant activities of chuangxinmycin and its derivatives against Mycobacterium tuberculosis, suggesting their potential for antituberculosis drug development.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Multidisciplinary
Felix Trottmann, Keishi Ishida, Mie Ishida-Ito, Hajo Kries, Michael Groll, Christian Hertweck
Summary: Bacteria of the Burkholderia pseudomallei group are a global health threat, causing infectious diseases. A conserved gene cluster in these bacteria is responsible for the synthesis of polyketides, which are critical for virulence. Researchers have discovered that an enzyme called BurG is involved in the formation of a cyclopropanol ring, providing insight into the biochemical basis of this process. This finding has important implications for the development of antivirulence strategies.
Review
Biotechnology & Applied Microbiology
Nur Farah Anis Abd Halim, Mohd Shukuri Mohamad Ali, Adam Thean Chor Leow, Raja Noor Zaliha Raja Abd Rahman
Summary: Fatty acid desaturase plays a crucial role in the synthesis of polyunsaturated fatty acids, with limited research on membrane fatty acid desaturases due to challenges in recombinant production. However, technological advancements have shown progress in elucidating the crystal structures of membrane fatty acid desaturases.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Houchao Xu, Jeroen S. Dickschat
Summary: This article provides a summary of known sesquiterpenes produced biogenetically from hedycaryol. The reasoning behind their absolute configurations is discussed. The analysis shows that reprotonations at the C1=C10 double bond of hedycaryol typically lead to 6-6 bicyclic compounds, while reprotonations at the C4=C5 double bond occur at C4 and result in 5-7 bicyclic compounds.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Jingxuan Tai, Lin Wang, Wai Shan Chan, Jiahui Cheng, Yuk Hei Chan, Marianne M. Lee, Michael K. Chan
Summary: Macrocyclization is an effective strategy to improve the stability and efficacy of protein therapeutics. In this study, a scalable and robust system based on endogenous biosynthesis of a noncanonical amino acid coupled with the pyrrolysine translational machinery is described for generating lasso-grafted proteins. With this system, cyclization of a therapeutic P16 peptide engrafted on a fusion protein was achieved in under 3 hours, resulting in improved binding affinity and serum stability.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Cailian Zhou, Jiao Feng, Jing Wang, Ning Hao, Xin Wang, Kequan Chen
Summary: Three artificial pathways were designed and successfully conducted to produce nicotinamide mononucleotide (NMN) in vitro. The adenosine phosphate hydrolysis (APH) pathway exhibited the highest level of NMN synthesis. By screening different enzymes and optimizing the catalysis system, the NMN titer was significantly increased. This is the first study to use a multienzyme cascade catalysis process for NMN biosynthesis.
CATALYSIS SCIENCE & TECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiaowei Pan, Jun Ma, Xiaodong Su, Peng Cao, Wenrui Chang, Zhenfeng Liu, Xinzheng Zhang, Mei Li
Article
Biochemistry & Molecular Biology
Haizhan Jiao, Yan Yin, Zhenfeng Liu
Article
Food Science & Technology
W. Zhang, X. Chang, Z. Wu, J. Dou, Y. Yin, C. Sun, W. Wu
WORLD MYCOTOXIN JOURNAL
(2020)
Review
Biochemistry & Molecular Biology
Peng Cao, Xiaowei Pan, Xiaodong Su, Zhenfeng Liu, Mei Li
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Danfeng Song, Haizhan Jiao, Zhenfeng Liu
Summary: MprF, a crucial family of membrane proteins in bacteria, enables pathogens like Staphylococcus aureus to acquire resistance to specific drugs and antimicrobial peptides. Cryo-EM structures of RtMprF in complex with LysPG reveal insights into the mechanisms of phospholipid modification and translocation.
NATURE COMMUNICATIONS
(2021)
Review
Plant Sciences
Xin Sheng, Zhenfeng Liu, Eunchul Kim, Jun Minagawa
Summary: Photosynthesis is the process by which plants and algae capture photons and store their energy through reactions in photosystem II (PSII). Recent studies on the architectures of PSII-LHCII supercomplexes in plants and green algae provide insights into the evolution of these complexes and their energy transfer pathways. The efficiency of photosynthesis largely depends on the initial reactions in PSII, involving light-harvesting and electron transfer mechanisms.
PLANT AND CELL PHYSIOLOGY
(2021)
Article
Biology
Yao Rong, Jinghui Jiang, Yiwei Gao, Jianli Guo, Danfeng Song, Wenhao Liu, Mingmin Zhang, Yan Zhao, Bailong Xiao, Zhenfeng Liu
Summary: TMEM120A, a member of the TMEM120 family, plays a key role in adipocyte differentiation, metabolism, and sensing mechanical pain by potentially functioning as an ion channel. The cryo-EM structures of human TMEM120A revealed a symmetrical homodimer with each monomer containing CoASH molecule, suggesting alternative roles in CoASH transport, sensing, or metabolism. Mutations affecting CoASH binding affinity in HsTMEM120A lead to distinct conformations in the presence or absence of CoASH.
Article
Multidisciplinary Sciences
Hao Liu, Anjie Li, Rochaix Jean-David, Zhenfeng Liu
Summary: Chloroplasts import nuclear-encoded proteins using translocon complexes in the outer and inner envelope membranes. The structure of the TOC-TIC supercomplex from Chlamydomonas reinhardtii has been determined, revealing the overall architecture and protein organization. The presence of an inositol hexaphosphate molecule and lipid molecules within the supercomplex suggests their role in stabilizing the assembly and supporting preprotein translocation.
Article
Biology
Asako Ishii, Jianyu Shan, Xin Sheng, Eunchul Kim, Akimasa Watanabe, Makio Yokono, Chiyo Noda, Chihong Song, Kazuyoshi Murata, Zhenfeng Liu, Jun Minagawa, David M. Kramer
Summary: Under low light conditions, Ostreococcus tauri assembles its photosystem I (PSI) supercomplex with light-harvesting complexes I (LHCI) and a prasinophyte-specific light-harvesting complex (Lhcp), expanding its photon-absorbing capacity. The structure of the supercomplex exhibits hybrid features of plant-type and green algal-type PSI supercomplexes. The formation of this supercomplex is likely induced by changes in light intensity through phosphorylation.
Article
Biochemistry & Molecular Biology
Bowei Yang, Hebang Yao, Dianfan Li, Zhenfeng Liu
Summary: Phosphatidylglycerol phosphate synthase (PgsA) plays a crucial role in pathogenic bacteria such as Staphylococcus aureus and mutations in PgsA are associated with resistance to daptomycin. The crystal structures of S. aureus PgsA reveal detailed insights into the catalytic process and provide a structural framework for the development of antimicrobial agents.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)
Article
Plant Sciences
Xiaowei Pan, Ryutaro Tokutsu, Anjie Li, Kenji Takizawa, Chihong Song, Kazuyoshi Murata, Tomohito Yamasaki, Zhenfeng Liu, Jun Minagawa, Mei Li
Summary: The study provides high-resolution structures of the PSI-LHCI-LHCII supercomplex from Chlamydomonas reinhardtii, elucidating the assembly mechanism between the PSI-LHCI complex and phosphorylated LHCII trimers, as well as the direct interactions between specific LhcbM isoforms and the PSI core. Functional studies on mutant strains lacking LhcbM1 or LhcbM5 demonstrate that only LhcbM5 is essential for supercomplex formation, revealing specific interactions and potential energy transfer pathways between green algal PSI and phosphorylated LHCIIs.
Article
Plant Sciences
Xin Sheng, Akimasa Watanabe, Anjie Li, Eunchul Kim, Chihong Song, Kazuyoshi Murata, Danfeng Song, Jun Minagawa, Zhenfeng Liu
Article
Plant Sciences
Xiaodong Su, Jun Ma, Xiaowei Pan, Xuelin Zhao, Wenrui Chang, Zhenfeng Liu, Xinzheng Zhang, Mei Li
Article
Biology
Xiaomin Ou, Jianli Guo, Longfei Wang, Hanting Yang, Xiuying Liu, Jianyuan Sun, Zhenfeng Liu
