Suppr超能文献

次生代谢产物基因组挖掘的最新进展(涵盖2012 - 2018年)

Recent advances in the genome mining of secondary metabolites (covering 2012-2018).

作者信息

Romsdahl Jillian, Wang Clay C C

机构信息

Department of Pharmacology and Pharmaceutical Sciences , School of Pharmacy , University of Southern California , 1985 Zonal Avenue , Los Angeles , CA 90089 , USA . Email:

Department of Chemistry , Dornsife College of Letters, Arts, and Sciences , University of Southern California , 3551 Trousdale Pkwy , Los Angeles , CA 90089 , USA.

出版信息

Medchemcomm. 2019 Apr 26;10(6):840-866. doi: 10.1039/c9md00054b. eCollection 2019 Jun 1.

Abstract

Secondary metabolites (SMs) produced by filamentous fungi possess diverse bioactivities that make them excellent drug candidates. Whole genome sequencing has revealed that fungi have the capacity to produce a far greater number of SMs than have been isolated, since many of the genes involved in SM biosynthesis are either silent or expressed at very low levels in standard laboratory conditions. There has been significant effort to activate SM biosynthetic genes and link them to their downstream products, as the SMs produced by these "cryptic" pathways offer a promising source for new drug discovery. Further, an understanding of the genes involved in SM biosynthesis facilitates product yield optimization of first-generation molecules and genetic engineering of second-generation analogs. This review covers advances made in genome mining SMs produced by , , , and in the past six years (2012-2018). Genetic identification and molecular characterization of SM biosynthetic gene clusters, along with proposed biosynthetic pathways, will be discussed in depth.

摘要

丝状真菌产生的次生代谢产物(SMs)具有多种生物活性,使其成为优秀的药物候选物。全基因组测序表明,真菌产生的SMs数量远多于已分离出来的数量,因为许多参与SM生物合成的基因在标准实验室条件下要么沉默,要么表达水平很低。人们已做出巨大努力来激活SM生物合成基因并将它们与其下游产物联系起来,因为这些“隐秘”途径产生的SMs为新药发现提供了一个有前景的来源。此外,了解参与SM生物合成的基因有助于优化第一代分子的产物产量以及对第二代类似物进行基因工程改造。本综述涵盖了过去六年(2012 - 2018年)在对曲霉属、青霉属、链霉菌属和木霉属产生的SMs进行基因组挖掘方面取得的进展。将深入讨论SM生物合成基因簇的遗传鉴定和分子特征,以及提出的生物合成途径。

相似文献

1
Recent advances in the genome mining of secondary metabolites (covering 2012-2018).
Medchemcomm. 2019 Apr 26;10(6):840-866. doi: 10.1039/c9md00054b. eCollection 2019 Jun 1.
2
Recent advances in genome mining of secondary metabolites in Aspergillus terreus.
Front Microbiol. 2014 Dec 23;5:717. doi: 10.3389/fmicb.2014.00717. eCollection 2014.
5
A genomics based discovery of secondary metabolite biosynthetic gene clusters in Aspergillus ustus.
PLoS One. 2015 Feb 23;10(2):e0116089. doi: 10.1371/journal.pone.0116089. eCollection 2015.
6
An efficient system for heterologous expression of secondary metabolite genes in Aspergillus nidulans.
J Am Chem Soc. 2013 May 22;135(20):7720-31. doi: 10.1021/ja401945a. Epub 2013 May 9.
7
Fungal secondary metabolites - strategies to activate silent gene clusters.
Fungal Genet Biol. 2011 Jan;48(1):15-22. doi: 10.1016/j.fgb.2010.04.004. Epub 2010 Apr 28.

引用本文的文献

1
Gene regulatory network resource aids in predicting trans-acting regulators of biosynthetic gene clusters in .
mBio. 2025 Mar 12;16(3):e0387424. doi: 10.1128/mbio.03874-24. Epub 2025 Feb 18.
4
Comparative metabolomics study on the secondary metabolites of the red alga, and its associated endosymbiotic fungi.
RSC Adv. 2024 Jun 20;14(26):18553-18566. doi: 10.1039/d4ra01055h. eCollection 2024 Jun 6.
5
Bioprospecting of sp. as a promising repository for anti-cancer agents: a comprehensive bibliometric investigation.
Front Microbiol. 2024 May 15;15:1379602. doi: 10.3389/fmicb.2024.1379602. eCollection 2024.
7
Small NRPS-like enzymes in sections and selectively form substituted pyrazinone metabolites.
Front Fungal Biol. 2022 Oct 26;3:1029195. doi: 10.3389/ffunb.2022.1029195. eCollection 2022.
8
Biosynthesis of Antibacterial Iron-Chelating Tropolones in as Response to Glycopeptide-Producing Streptomycetes.
Front Fungal Biol. 2022 Jan 3;2:777474. doi: 10.3389/ffunb.2021.777474. eCollection 2021.
9
Expanding the Chemical Diversity of Secondary Metabolites Produced by Two Marine-Derived Enterocin- and Wailupemycin-Producing Strains.
ACS Omega. 2023 Jul 29;8(31):28886-28897. doi: 10.1021/acsomega.3c04199. eCollection 2023 Aug 8.

本文引用的文献

1
Identification of the Pyranonigrin A Biosynthetic Gene Cluster by Genome Mining in IBT 5891.
AIChE J. 2018 Dec;64(12):4182-4186. doi: 10.1002/aic.16324. Epub 2018 Jun 11.
2
Hybrid Transcription Factor Engineering Activates the Silent Secondary Metabolite Gene Cluster for (+)-Asperlin in Aspergillus nidulans.
ACS Chem Biol. 2018 Nov 16;13(11):3193-3205. doi: 10.1021/acschembio.8b00679. Epub 2018 Oct 29.
4
Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.
Nature. 2018 Jul;559(7714):415-418. doi: 10.1038/s41586-018-0319-4. Epub 2018 Jul 11.
5
Asperphenamate biosynthesis reveals a novel two-module NRPS system to synthesize amino acid esters in fungi.
Chem Sci. 2018 Jan 24;9(9):2589-2594. doi: 10.1039/c7sc02396k. eCollection 2018 Mar 7.
6
Linking secondary metabolites to gene clusters through genome sequencing of six diverse species.
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E753-E761. doi: 10.1073/pnas.1715954115. Epub 2018 Jan 9.
9
Bacterial Branched-Chain Amino Acid Biosynthesis: Structures, Mechanisms, and Drugability.
Biochemistry. 2017 Nov 7;56(44):5849-5865. doi: 10.1021/acs.biochem.7b00849.
10
Fungal and Bacterial Pigments: Secondary Metabolites with Wide Applications.
Front Microbiol. 2017 Jun 22;8:1113. doi: 10.3389/fmicb.2017.01113. eCollection 2017.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验