Article
Plant Sciences
Xiaomeng Hao, Shasha Li, Guiyang Wang, Jianrui Li, Zonggen Peng, Yuqin Zhang, Liyan Yu, Maoluo Gan
Summary: Two new cyclic octapeptides and four analogues were identified from an endophytic Kitasatospora sp. CPCC 204717, showing potent antibacterial and antiviral activities.
JOURNAL OF NATURAL PRODUCTS
(2022)
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
Plant Sciences
Ziwei Yao, Changli Sun, Yuhui Xia, Fang Wang, Liwu Fu, Junying Ma, Qinglian Li, Jianhua Ju
Summary: By precursor-directed biosynthesis, ten new actinomycin analogues were produced with impressive antimicrobial activities against clinically derived antibiotic resistant pathogens, including Staphylococcus aureus, Enterococcus faecium, and Candida albicans, while showing low cytotoxicity.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Organic
Lea Winand, Pascal Schneider, Sebastian Kruth, Nico-Joel Greven, Wolf Hiller, Marcel Kaiser, Joerg Pietruszka, Markus Nett
Summary: By combining chemical synthesis with pathway refactoring, a series of physostigmine analogues with altered specificity and toxicity profiles were produced in the heterologous host. Among the compounds generated, the promising drug candidate phenserine was included, which was previously only accessible through total synthesis. This study provides a new approach for the development of novel therapeutics.
Article
Biotechnology & Applied Microbiology
Miaomiao Yin, Dongliang Xiao, Chen Wang, Liwen Zhang, Baoqing Dun, Qun Yue
Summary: The global regulator LaeA positively regulates the production of Beauvericin, bassiatin, and various bioactive primary metabolites. Deletion of the BbLaeA gene leads to a decrease in Beauvericin production, while overexpression of the BbLaeA gene increases its production. In addition, overexpression of BbLaeA also increases the production of bassiatin and other primary metabolites.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Myoun-Su Kim, Munhyung Bae, Ye-Eun Jung, Jung Min Kim, Sunghoon Hwang, Myoung Chong Song, Yeon Hee Ban, Eun Seo Bae, Suckchang Hong, Sang Kook Lee, Sun-Shin Cha, Dong-Chan Oh, Yeo Joon Yoon
Summary: The biosynthesis of cyclodepsipeptide WS9326A in Streptomyces sp. SNM55 involves unprecedented nonlinear NRPS assembly processes, including the shuttling of activated amino acids mediated by TE enzymes, the independent operation of C-T didomain modules, and the first example of module skipping.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Plant Sciences
Ning Mu, Heng Guo, E. Zhang, Yu Yin, Wengui Wang, Dandan Chen, Shoufeng Wang, Wen Liu
Summary: By using mutational biosynthesis, researchers introduced benzothiophene into nosiheptide biosynthetic pathway and generated three bioactive analogues with benzothiophene-containing side rings. These analogues effectively increase the yield and activity of S-NOS-1 against Gram-positive pathogens.
JOURNAL OF NATURAL PRODUCTS
(2022)
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.
Review
Chemistry, Multidisciplinary
Carter N. Stout, Hans Renata
Summary: Biocatalytic transformations are powerful tools for constructing complex natural products, enabling the incorporation of stereochemistry in synthetic campaigns. By leveraging enzymes, synthetic chemists can expand the chiral pool and simplify synthesis processes.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
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
Xueyang Ma, Zhijun Tang, Wenping Ding, Tan Liu, Donghui Yang, Wen Liu, Ming Ma
Summary: Recruitment of trans-acting enzymes by non ribosomal peptide synthetase (NRPS) assembly line is rare. In collismycin biosynthesis, ColB1, a flavin-dependent dehydrogenase, is recruited by an NRPS terminal condensation domain (Ct domain) and catalyzes peptidyl carrier protein (PCP)-tethered cysteine dehydrogenation. The crystal structure of ColB1 complexed with FAD reveals distinct structural features from acyl-CoA dehydrogenases (ACADs) in substrate recognition. A Glu393-mediated catalytic mechanism is established, where the cysteine substrate is sandwiched between Glu393 and FAD. A ColB1-PCP-Ct complex model provides insights into the unique recruitment interactions between ColB1 and associated NRPS.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Physical
Qiyao Shen, Haibo Zhou, Guangzhi Dai, Guannan Zhong, Liujie Huo, Aiying Li, Yang Liu, Ming Yang, Vinothkannan Ravichandran, Zhihui Zheng, Ya-Jie Tang, Nianzhi Jiao, Youming Zhang, Xiaoying Bian
Summary: The biosynthetic mechanism of polythiazole in microbial nonribosomal peptides (NRPs) has been uncovered, revealing the involvement of a cryptic NRPS gene cluster. The study also showed that the oxidation of polythiazole in NRPs is not catalyzed by integrated oxidase domains as previously believed, but by a standalone oxidase.
Review
Biochemistry & Molecular Biology
Akimasa Miyanaga, Fumitaka Kudo, Tadashi Eguchi
Summary: Adenylation (A) domains are essential for the biosynthesis of nonribosomal peptides and related natural products. They selectively transfer acyl substrates onto cognate carrier proteins, expanding the structural diversity of natural products. Interrupted A domains with embedded auxiliary domains can modify the incorporated acyl units.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lauren A. Washburn, Keshav K. Nepal, Coran M. H. Watanabe
Summary: The study developed a strategy to trap and characterize enzyme intermediates bound by a thioester bond, successfully applying it to the azinomycin and colibactin biosynthetic pathways.
ACS CHEMICAL BIOLOGY
(2021)
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
Biotechnology & Applied Microbiology
Laszlo Kozak, Zoltan Szilagyi, Laszlo Toth, Istvan Pocsi, Istvan Molnar
FOLIA MICROBIOLOGICA
(2020)
Article
Agriculture, Multidisciplinary
Peng-Fei Hu, Jing Huang, Lei Chen, Zhongyang Ding, Liming Liu, Istvan Molnar, Bo-Bo Zhang
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2020)
Article
Microbiology
Mu Li, Lijing Kang, Xiaoli Ding, Jiao Liu, Qingpei Liu, Yanchun Shao, Istvan Molnar, Fusheng Chen
Article
Food Science & Technology
Ying-Ying Huang, Zhang-Cheng Liang, Xiao-Zi Lin, Zhi-Gang He, Xiang-Yun Ren, Wei-Xin Li, Istvan Molnar
Summary: This study investigated the fungal microbiome compositions of Hong Qu glutinous rice wine and identified key fungi responsible for fermentation characteristics. The findings showed significant differences in fermentation characteristics among different regional varieties of HQ, providing valuable insights for controlling fungal community structures and designing fermentation processes for HQ wines with desirable characteristics.
FOOD RESEARCH INTERNATIONAL
(2021)
Article
Microbiology
Linan Xie, Dongliang Xiao, Xiaojing Wang, Chen Wang, Jing Bai, Qun Yue, Haitao Yue, Ye Li, Istvan Molnar, Yuquan Xu, Liwen Zhang
Article
Microbiology
Qingpei Liu, Siyu Zhong, Xinrui Wang, Shuaibiao Gao, Xiaolong Yang, Fusheng Chen, Istvan Molnar
Summary: Monascus-type azaphilone pigments (MonAzPs) are widely used in East Asia as food colorants and nutraceuticals, with a highly complex biosynthetic pathway and gene clusters. This study uses computational and transcriptional analyses to predict and validate the extent of the MonAzPs biosynthetic gene cluster in Monascus ruber M7, highlighting the need for comprehensive approaches to determine secondary metabolite gene cluster boundaries accurately. Additionally, orthologous but non-syntenic MonAzPs biosynthetic gene clusters were predicted in two strains of Talaromyces marneffei, showcasing variability in this gene cluster among different fungi.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ya-ming Xu, Chandrashekhar Madasu, Manping X. Liu, E. M. Kithsiri Wijeratne, David Dierig, Bob White, Istvan Molnar, A. A. Leslie Gunatilaka
Summary: A total of 12 new cycloartane- and lanostane-type triterpenoids, along with 10 known triterpenoids, were isolated from the resin of Parthenium argentatum AZ-2 obtained as a byproduct of Bridgestone guayule rubber production. Compounds 13, 14, and 18 exhibited weak cytotoxic activity for several cancer cell lines.
Article
Chemistry, Medicinal
Chandrashekhar Madasu, Ya-Ming Xu, E. M. Kithsiri Wijeratne, Manping X. Liu, Istvan Molnar, A. A. Leslie Gunatilaka
Summary: Argentatins A-C, the major cycloartane-type triterpenoids in guayule resin, were converted into pyrimidine, thiazole, and indole analogues. The cytotoxic activities of these analogues were compared with the parent compounds against cancer cell lines and normal cells, showing enhanced activity in the pyrimidine analogues. These findings suggest the potential of triterpenoid constituents in guayule resin for anticancer drug discovery.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Chen Wang, Dongliang Xiao, Baoqing Dun, Miaomiao Yin, Adigo Setargie Tsega, Linan Xie, Wenhua Li, Qun Yue, Sibao Wang, Han Gao, Min Lin, Liwen Zhang, Istvan Molnar, Yuquan Xu
Summary: A unique group of nonribosomal peptide secondary metabolites, called xylomyrocins, have been discovered in fungi. The biosynthesis of these compounds is linked to carbohydrate catabolism and involves polyspecificity in the terminal condensation domain of nonribosomal peptide synthetase enzymes. The study also found rare promiscuous methylation in the context of an otherwise canonical biosynthetic program.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Qingpei Liu, Dan Zhang, Shuaibiao Gao, Xianhua Cai, Ming Yao, Yao Xu, Yifu Gong, Ke Zheng, Yigui Mao, Liyan Yang, Dengfeng Yang, Istvan Molnar, Xiaolong Yang
Summary: It was found that Orsellinic acid (OA) derivatives are synthesized by filamentous fungi using nonreducing polyketide synthases (nrPKSs). The chain-releasing thioesterase (TE) domains of such nrPKSs were proposed to also catalyze dimerization to yield didepsides, such as lecanoric acid. Through combinatorial domain exchanges, domain dissections and reconstitutions, it was revealed that the TE domain of the lecanoric acid synthase Preu6 of Preussia isomera must collaborate with the starter acyl transferase (SAT) domain from the same nrPKS. Artificial SAT-TE fusion proteins were shown to be highly effective catalysts and able to reprogram the ketide homologation chassis to form didepsides. The dissected SAT and TE domains of Preu6 were also demonstrated to physically interact, indicating the potential co-evolution of SAT and TE domains in OA-synthesizing nrPKSs. This study highlights an unexpected domain-domain interaction in nrPKSs and its significance in the biosynthesis of unnatural didepsides, depsidones, and diphenyl ethers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Liwen Zhang, Chen Wang, Kang Chen, Weimao Zhong, Yuquan Xu, Istvan Molnar
Summary: Fungal nonribosomal peptides (NRPs) and polyketide-nonribosomal peptide hybrid products (PK-NRPs) are valuable sources of bioactive compounds. The synthesis of these complex natural products involves nonribosomal peptide synthetases (NRPSs) and polyketide synthase modules, which can be reprogrammed to generate novel bioactive peptides and PK-NRPs. Recent advances have been made in the discovery and engineering of fungal NRPS assembly lines, but challenges remain in understanding the complexities of fungal NRP and PK-NRP biosynthesis.
NATURAL PRODUCT REPORTS
(2023)
Article
Biotechnology & Applied Microbiology
Yu-Ping Huang, Jie-Yan Shi, Si-Chen Luo, Shao-Yan Xu, Jia-Dong Zhang, Istvan Molnar, Qiong-Qiong Yang, Bo-Bo Zhang
Summary: This study found that acetic acid and lactic acid in the cell-free supernatant of L. rhamnosus inhibit the growth of G. vaginalis by altering the morphology of the bacteria and affecting their ATP synthesis. The results provide valuable information for the use of L. rhamnosus in the treatment of bacterial vaginosis.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2023)
Article
Microbiology
Ayako Kusakabe, Chen Wang, Ya-Ming Xu, Istvan Molnar, S. Patricia Stock
Summary: This study discovered three secondary metabolites with nematicidal and nematistatic activities from Photorhabdus strain Caborca. These metabolites showed selective effects against two important plant parasitic nematodes, root-knot nematode and citrus nematode. The combination of all three metabolites showed a synergistic effect on nematode control, while other combinations had compound- and nematode-dependent interactions.
MICROBIOLOGY SPECTRUM
(2022)
Review
Biochemistry & Molecular Biology
Liwen Zhang, Qun Yue, Chen Wang, Yuquan Xu, Istvan Molnar
NATURAL PRODUCT REPORTS
(2020)
Review
Biochemistry & Molecular Biology
Liwen Zhang, Opemipo Esther Fasoyin, Istvan Molnar, Yuquan Xu
NATURAL PRODUCT REPORTS
(2020)
