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进化基因组挖掘在天然产物生物合成的发现和工程中的应用。

Evolutionary Genome Mining for the Discovery and Engineering of Natural Product Biosynthesis.

机构信息

Wisconsin Institute for Discovery and Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI, USA.

Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Guanajuato, Mexico.

出版信息

Methods Mol Biol. 2022;2489:129-155. doi: 10.1007/978-1-0716-2273-5_8.

DOI:10.1007/978-1-0716-2273-5_8
PMID:35524049
Abstract

Genome mining has become an invaluable tool in natural products research to quickly identify and characterize the biosynthetic pathways that assemble secondary or specialized metabolites. Recently, evolutionary principles have been incorporated into genome mining strategies in an effort to better assess and prioritize novelty and understand their chemical diversification for engineering purposes. Here, we provide an introduction to the principles underlying evolutionary genome mining, including bioinformatic strategies and natural product biosynthetic databases. We introduce workflows for traditional genome mining, focusing on the popular pipeline antiSMASH, and methods to predict enzyme substrate specificity from genomic information. We then provide an in-depth discussion of evolutionary genome mining workflows, including EvoMining, CORASON, ARTS, and others, as adopted by our group for the discovery and prioritization of natural products biosynthetic gene clusters and their products.

摘要

基因组挖掘已成为天然产物研究中一种非常宝贵的工具,可以快速鉴定和描述组装次生代谢物或特殊代谢物的生物合成途径。最近,进化原理已被纳入基因组挖掘策略中,以更好地评估和优先考虑新颖性,并理解其用于工程目的的化学多样化。在这里,我们介绍了进化基因组挖掘的基本原则,包括生物信息学策略和天然产物生物合成数据库。我们介绍了传统基因组挖掘的工作流程,重点介绍了流行的 pipeline antiSMASH,并介绍了从基因组信息预测酶底物特异性的方法。然后,我们深入讨论了进化基因组挖掘工作流程,包括我们小组用于发现和优先考虑天然产物生物合成基因簇及其产物的 EvoMining、CORASON、ARTS 等方法。

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本文引用的文献

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The Design-Build-Test-Learn cycle for metabolic engineering of Streptomycetes.用于链霉菌代谢工程的设计-构建-测试-学习循环。
Essays Biochem. 2021 Jul 26;65(2):261-275. doi: 10.1042/EBC20200132.
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Evolution of combinatorial diversity in trans-acyltransferase polyketide synthase assembly lines across bacteria.细菌中转酰基转移酶聚酮合酶装配线中组合多样性的演变。
Nat Commun. 2021 Mar 3;12(1):1422. doi: 10.1038/s41467-021-21163-x.
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Tiny Earth: A Big Idea for STEM Education and Antibiotic Discovery.微小世界:STEM 教育和抗生素发现的伟大创意。
mBio. 2021 Feb 16;12(1):e03432-20. doi: 10.1128/mBio.03432-20.
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BiG-SLiCE: A highly scalable tool maps the diversity of 1.2 million biosynthetic gene clusters.BiG-SLiCE:一个高度可扩展的工具,可绘制 120 万个生物合成基因簇的多样性图谱。
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Nucleic Acids Res. 2021 Jan 8;49(D1):D1020-D1028. doi: 10.1093/nar/gkaa1105.
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The antiSMASH database version 3: increased taxonomic coverage and new query features for modular enzymes.反 SMASH 数据库版本 3:增加了分类学覆盖范围和新的模块酶查询功能。
Nucleic Acids Res. 2021 Jan 8;49(D1):D639-D643. doi: 10.1093/nar/gkaa978.
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dbCAN-PUL: a database of experimentally characterized CAZyme gene clusters and their substrates.dbCAN-PUL:一个经过实验验证的 CAZyme 基因簇及其底物数据库。
Nucleic Acids Res. 2021 Jan 8;49(D1):D523-D528. doi: 10.1093/nar/gkaa742.
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New developments in RiPP discovery, enzymology and engineering.RiPP 发现、酶学和工程的新进展。
Nat Prod Rep. 2021 Jan 1;38(1):130-239. doi: 10.1039/d0np00027b. Epub 2020 Sep 16.
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RRE-Finder: a Genome-Mining Tool for Class-Independent RiPP Discovery.RRE-Finder:一种用于发现与类别无关的核糖体合成和翻译后修饰肽的基因组挖掘工具。
mSystems. 2020 Sep 1;5(5):e00267-20. doi: 10.1128/mSystems.00267-20.