Review
Biochemistry & Molecular Biology
Shaheera Tabassum, Ameer Fawad Zahoor, Sajjad Ahmad, Razia Noreen, Samreen Gul Khan, Hamad Ahmad
Summary: Cross-coupling reactions are powerful tools for synthesizing natural products, with Suzuki, Negishi, Heck, Sonogashira, and Stille reactions being commonly used in total synthesis. This review highlights the significance of these reactions in organic synthesis and provides examples of incorporating multiple types of cross-coupling reactions in the synthesis of natural products.
MOLECULAR DIVERSITY
(2022)
Article
Chemistry, Multidisciplinary
Kaho Sogahata, Taro Ozaki, Yuya Igarashi, Yuka Naganuma, Chengwei Liu, Atsushi Minami, Hideaki Oikawa
Summary: UstYa family proteins are widely distributed in fungi and are involved in the biosynthesis of peptides. Three UstYa homologues were found to be crucial for desaturation of amino acid moieties, displaying unique functions. Further research could lead to the discovery of novel fungal metabolites with unique modifications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Xiaojun Li, Ryo Shimaya, Tohru Dairi, Wei-chen Chang, Yasushi Ogasawara
Summary: The study identified the biosynthetic pathways of peptide natural products Hormaomycins and Belactosins, revealing a novel pathway for cyclopropane ring construction and exemplifying new chemistry involving metalloenzymes in natural product biosynthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Florian Hubrich, Nina M. Bosch, Clara Chepkirui, Brandon Morinaka, Michael Rust, Muriel Gugger, Serina L. Robinson, Anna L. Vagstad, Jorn Piel
Summary: Lipopeptides are a group of microbial natural products that are important for their antibacterial and antifungal properties, as well as their strong biosurfactant effects. Most lipopeptides consist of cyclic peptides with various fatty acyl groups at the N-terminus. In this study, ribosomally derived lipopeptides called selidamides were discovered through genome-guided approaches. These selidamides were found to be widely distributed across different bacterial phyla and have cyclic peptide moieties with fatty acyl units attached to ornithine or lysine side chains. Unlike nonribosomal lipopeptides, selidamides are selectively acylated with different fatty acids. This study highlights the ability of ribosomal pathways to produce diverse lipopeptides and expands the potential for peptide drug development and targeted discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Mugilarasi Purushothaman, Snigdha Sarkar, Maho Morita, Muriel Gugger, Eric W. Schmidt, Brandon I. Morinaka
Summary: Genome mining was used to identify a novel cyanobactin metabolite tolypamide from the freshwater cyanobacterium Tolypothrix sp., which features an unprecedented post-translational prenylation modification on a threonine residue. The enzyme TolF shows strict selectivity for prenylation of serine or threonine, providing potential as a robust tool for synthetic biology.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
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
Chemistry, Multidisciplinary
Hui Tao, Takahiro Mori, Xingxing Wei, Yudai Matsuda, Ikuro Abe
Summary: This study investigated the biosynthesis mechanism of Calbistrins through heterologous and in vitro reconstitution, as well as a structural biological study. The analysis revealed that the decalin and polyene portions of Calbistrins are synthesized by the single PKS CalA, with the aid of the enzymes CalK and CalH. Additionally, the esterification of the two polyketide parts is catalyzed by the acyltransferase CalD, uncovering a novel dual-functional PKS and broadening the understanding of fungal synthesis of diverse polyketide natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biochemistry & Molecular Biology
Vincent Courdavault, Sarah E. O'Connor, Michael K. Jensen, Nicolas Papon
Summary: Plant natural products are essential for human health, but their complex structures make profitable production through total chemical synthesis difficult. Hence, industrial processes still rely on extraction from plant materials. Advances in biotechnological manufacturing have led to significant progress in producing PNPs in heterologous hosts.
NATURAL PRODUCT REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Dongqi Yi, Vinayak Agarwal
Summary: Natural products containing the alpha-pyrone moiety are produced by polyketide synthases (PKSs) in bacteria, fungi, and plants. This study demonstrates that truncating a tetraketide natural product producing PKS assembly line allows for a thioesterase-independent off-loading of an alpha-pyrone polyketide natural product. By engineering the truncated PKS in vitro, it is shown that a ketosynthase (KS) domain with relaxed substrate selectivity can expand the chemical space of alpha-pyrone polyketide natural products.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yuchen Li, Seoung Rak Lee, Esther J. Han, Mohammad R. Seyedsayamdost
Summary: Natural products are important sources of pharmaceuticals and chemical tools. This study focused on the discovery of new natural products from well-studied strains, specifically targeting Streptomyces rimosus, a widely-used oxytetracycline producer. Through MALDI-MS-guided high-throughput elicitor screening (HiTES), the researchers mapped the metabolome of S. rimosus and characterized three cryptic biosynthetic gene clusters, including the unusual cyclic peptide natural product momomycin. The study demonstrated that HiTES is an effective approach for finding new chemical matter from drained strains.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biotechnology & Applied Microbiology
Peishan Li, Shufen He, Xuejiao Zhang, Qi Gao, Yanan Liu, Liwei Liu
Summary: Prodiginines are a diverse group of microbial secondary metabolites with various biological activities. Despite the focus on the star molecule prodigiosin, little is known about other prodiginine members, limiting their research and application. This review provides insights into the prodiginine family and serves as a guideline for new research.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yutong Li, Linlin Zhang, Wang Wang, Yang Liu, Dejuan Sun, Hua Li, Lixia Chen
Summary: Cage-like compounds found in natural products have diverse structures and significant biological activities, playing an important role in drug discovery. The development and utilization of these compounds have become a research hotspot in the fields of chemistry and biology.
BIOORGANIC CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Jackson K. B. Cahn, Jorn Piel
Summary: This review discusses available and emerging techniques for targeted single-cell analysis, with a particular focus on applications to the discovery and study of natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biotechnology & Applied Microbiology
Sebastian L. Wenski, Sirinthra Thiengmag, Eric J. N. Helfrich
Summary: Complex peptide natural products have diverse functions and properties, and can be biosynthesized through ribosomally synthesized and post-translationally modified peptide (RiPP) biosynthetic pathways and non-ribosomal peptide synthetases (NRPSs). Understanding these pathways has led to universal principles for targeted identification of peptide biosynthetic blueprints and rational engineering of biosynthetic pathways. This review contrasts the key principles of both routes and compares different strategies for peptide modifications.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2022)
Review
Chemistry, Applied
Antonio Del Rio Flores, Colin C. Barber, Maanasa Narayanamoorthy, Di Gu, Yuanbo Shen, Wenjun Zhang
Summary: Natural products are biologically produced compounds that play important roles in various biological processes. The biosynthetic pathways and potential applications of isonitrile and alkyne functionalities are still not fully understood. Understanding these pathways is crucial for rational design of biogenic molecules with these functionalities.
ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING
(2022)
Article
Multidisciplinary Sciences
Bidhan Chandra De, Wenjun Zhang, Chunfang Yang, Attila Mandi, Chunshuai Huang, Liping Zhang, Wei Liu, Mark W. Ruszczycky, Yiguang Zhu, Ming Ma, Ghader Bashiri, Tibor Kurtan, Hung-wen Liu, Changsheng Zhang
Summary: Epoxide ring opening reactions are important in both biological processes and synthetic applications. Flavins are shown to catalyze both reductive and oxidative epoxide ring opening reactions, and the underlying mechanisms are proposed.
NATURE COMMUNICATIONS
(2022)
Article
Criminology & Penology
Bo Wang
Summary: The Law Commission has proposed a new offence of cyberflashing, but its proposal lacks comprehensive evaluation of existing law and fails to balance the harm of a criminal conviction against the potential harm of cyberflashing. Modifying existing communication offences or harassment offences would offer more protection to victims.
JOURNAL OF CRIMINAL LAW
(2023)
Article
Chemistry, Multidisciplinary
Bin Tan, Qingbo Zhang, Ji Xiao, Chengshan Yuan, Yuchan Chen, Siqiang Chen, Weimin Zhang, Yiguang Zhu, Changsheng Zhang
Summary: In this study, the function of LobP1, a P450 monooxygenase encoded in the LOB biosynthetic gene cluster, was investigated through in vivo deletion and in vitro biochemical assays. LobP1 was shown to have a broad substrate scope, with a preference for substrates with a nitrosugar. The new LOBs derivatives exhibited significant antibacterial and cytotoxic activities against various bacteria and cancer cell lines.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Xuemin Ding, Weixia Ye, Bin Tan, Qiaoyun Song, Yuchan Chen, Wei Liu, Lili Sun, Wei Tang, Yulei Qiao, Qingbo Zhang, Haibo Zhang, Ying Wang, Weimin Zhang, Changsheng Zhang, Wenjun Zhang
Summary: Three new cytochalasins, talachalasins A-C (1-3), were discovered from a deep-sea-derived fungus called Talaromyces muroii sp. SCSIO 40439. The structures and absolute configurations of 1-3 were determined using various analytical techniques. Talachalasins A-C (1-3) are unique cytochalasans with a 168-methyl group, which distinguishes them from over 500 known CYTs. Talachalasin C (3) is a novel 20,21-seco-cytochalasans with a 2-oxabicyclo-[3.3.1]nonan-3-one unit. Talachalasin A (1) exhibited moderate cytotoxic activity against four tumor cell lines (IC50: 3.40-10.02 μM). Talachalasin B (2) demonstrated comparable anti-RSV and HSV-1 activities (IC50: 12.5 p.M or IC50: 20.0 μM).
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Plant Sciences
Bin Tan, Qingbo Zhang, Jieyi Li, Yiguang Zhu, Liping Zhang, Wenjun Zhang, Haibo Zhang, Yang Chen, Changsheng Zhang
Summary: The installation of halogen atoms into aromatic and less activated polyketide substrates by halogenases is a powerful strategy to tune the bioactivity, bioavailability, and reactivity of compounds. In this study, the halogenase TotH was confirmed to catalyze the C-4 chlorination in the biosynthetic pathway of totopotensamide A (1), leading to the formation of ClMeDPG. Six new deschloro totopotensamide (TPM) congeners TPMs H2-H7 (5-10) were isolated and their structures were elucidated. Additionally, the cytotoxicity of compounds 5, 6, 8, and 9 against several cell lines was evaluated.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Plant Sciences
Cunlei Cai, Yingying Chen, Le Zhou, Naying Gong, Hua Zhang, Changli Sun, Junying Ma, Jianhua Ju
Summary: Three diphenyl ethers (1-3) and a cyclopentenone (4), along with seven known compounds (5-11), were isolated from the fermentation broth of the marine sediment-derived fungus Spiromastix sp. SCSIO F190. Compound 3 and 4 exist as atropisomers and racemates, respectively. These compounds showed activities against various pathogenic bacteria, with compounds 1-4 exhibiting strong activity against Gram-positive bacteria, including methicillin-resistant strains.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Ziqian Cheng, Qingbo Zhang, Jing Peng, Xiaoyang Zhao, Liang Ma, Changsheng Zhang, Yiguang Zhu
Summary: In this study, a benzoxazole alkaloid-encoding biosynthetic gene cluster (mich BGC) was identified in the marine-derived actinomycete Micromonospora sp. SCSIO 07395 and heterologously expressed in Streptomyces albus. This led to the discovery of five new benzoxazole alkaloids microechmycin A-E (1-5) and a previously synthesized compound 6. Their structures were elucidated using HRESIMS and 1D and 2D NMR data. Microechmycin A (1) exhibited moderate antibacterial activity against Micrococcus luteus SCSIO ML01 with a minimal inhibitory concentration (MIC) value of 8 μg/mL.
Article
Chemistry, Multidisciplinary
Bin Tan, Liping Zhang, Qingbo Zhang, Siqiang Chen, Weiliang Xiong, Yiguang Zhu, Changsheng Zhang
Summary: This study identified a new environmental resistance determinant, the lobophorin (LOB) resistance-related glycosidase KijX, which has an unexpected correlation with the host-dependent chemical diversity of LOBs. KijX homologues are widely found among bacteria, archaea, and fungi, and they encode the same glycohydrolytic activity on LOBs. The crystal structure of a KijX homologue, AcvX, revealed its ability to accommodate and deglycosylate LOBs. This study highlights the importance of KijX-related glycosidases as preexisting resistance determinants and provides insight into the integration of resistance genes into natural product assembly.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Plant Sciences
Lijuan Wang, Mengyi Zhu, Qingbo Zhang, Shilan Zhai, Yiguang Zhu, Haibo Zhang, Changsheng Zhang
Summary: In this study, an alternative biological route to produce structurally diverse fidaxomicin aglycones was developed by refactoring the promoter and expressing it in a different host. The resulting titers of the five fidaxomicin aglycones ranged from 4.9 to 15.0 mg L-1. Overall, these findings demonstrate the potential of using a biological strategy to construct and diversify fidaxomicin aglycones.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemical Research Methods
Mengyi Zhu, Lijuan Wang, Haibo Zhang, Liping Zhang, Bin Tan, Qi Huang, Yiguang Zhu, Changsheng Zhang
Summary: Ribosome-targeting oligosaccharides, everninomicins (EVNs), are promising drug leads with a unique mode of action. By duplicating the biosynthetic gene cluster (BGC) in Micromonospora sp. SCSIO 07395, the production of EVNs was enhanced, allowing for bioactivity evaluation. EVNs showed significant inhibition against multidrug-resistant bacteria, with potency comparable or superior to vancomycin, linezolid, and daptomycin. The BGC duplication strategy successfully increased the titer of bioactive EVN M from trace amounts to 98.6 mg L-1, demonstrating the utility of a bioengineering approach for enhanced production and chemical diversification of EVNs.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Engineering, Marine
Ganesan Govindarajan, Ziwei Yao, Zhenbin Zhou, Xiaohong Zheng, Junying Ma, Pachaiyappan Saravana Kumar, Jianhua Ju, Changli Sun
Summary: In this study, the researchers sequenced the whole genome of Streptomyces griseus SCSIO PteL053, which was associated with the marine gastropod mollusk Planaxis sp. They discovered 28 putative biosynthetic gene clusters, including two responsible for the synthesis of therapeutic metabolites. Through detailed bioinformatics analysis, they identified the functions of the involved genes in the biosynthesis of known compounds. This complete genome sequencing allowed the rediscovery of clinically useful secondary metabolites in the newly isolated Streptomyces griseus.
JOURNAL OF MARINE SCIENCE AND ENGINEERING
(2023)
Article
Microbiology
Yingying Chen, Jiafan Yang, Cunlei Cai, Junjie Shi, Yongxiang Song, Junying Ma, Jianhua Ju
Summary: Marine-derived fungi are valuable sources of structurally novel natural products with diverse bioactivities. Recyclable markers, such as pyrG and amdS, were successfully established and applied in two marine-derived fungi, Aspergillus sp. SCSIO SX7S7 and Spiromastix sp. SCSIO F190, respectively. These markers allowed the construction of markerless strains and facilitated genome mining for novel compounds.
Article
Chemistry, Multidisciplinary
Peng Jiang, Hongbo Jin, Guangtao Zhang, Wenjun Zhang, Wei Liu, Yiguang Zhu, Changsheng Zhang, Liping Zhang
Summary: This study provides mechanistic understanding of the functional differences between the homologous cytochrome P450 enzymes IkaD and CftA, which catalyze multiple C-H oxidations on the same substrate with distinct regio- and chemoselectivity. The crystal structures reveal that the differences in the conformation of the F/G region in IkaD and CftA control the substrate orientation and determine their binding patterns with polar moieties. Fine-tuning the polar subpocket of IkaD can alter its regioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Plant Sciences
Xiaoyang Zhao, Youzhe Chen, Ting Long, Zhiying Liu, Qingbo Zhang, Haibo Zhang, Yan Yan, Changsheng Zhang, Yiguang Zhu
Summary: In this study, a depsidone encoding gene cluster from Ovatospora sp. SCSIO SY280D was heterologously reconstituted in Aspergillus nidulans A1145, resulting in the production of mollicellins, a representative family of depsidones. Furthermore, a bifunctional P450 monooxygenase that catalyzes both ether formation and hydroxylation in the biosynthesis of the mollicellins was discovered. The functions of a decarboxylase and an aromatic prenyltransferase were also characterized to understand the tailoring modification steps. This work provides important insights into the biosynthesis of mollicellins.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Organic
Zhuangjie Fang, Qingbo Zhang, Weiliang Xiong, Lili Sun, Bin Tan, Mengyi Zhu, Liang Ma, Liping Zhang, Yiguang Zhu, Changsheng Zhang
Summary: In this study, four new tetronate antibiotics called kongjuemycins (KJMs) were discovered from a coral-associated actinomycete. The biosynthetic gene cluster responsible for KJMs production was identified and characterized through various experiments. It was found that KJM biosynthesis utilizes diverse precursors from primary metabolism.
