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在基因组时代:从分类学到新抗菌次级代谢产物的发现。

in the genomic era: from taxonomy to the discovery of new antimicrobial secondary metabolites.

机构信息

Departamento de Genética and Programa de Pós-graduação em Genética e Biologia Molecular, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

Department for Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Tübingen, Germany.

出版信息

Crit Rev Microbiol. 2022 Mar;48(2):121-160. doi: 10.1080/1040841X.2021.1946009. Epub 2021 Aug 4.

DOI:10.1080/1040841X.2021.1946009
PMID:34346791
Abstract

Species of are highly versatile being found not only abundantly in soil, but also as plants and animals' commensals or pathogens. Their complex multireplicon genomes harbour an impressive number of polyketide synthase (PKS) and nonribosomal peptide-synthetase (NRPS) genes coding for the production of antimicrobial secondary metabolites (SMs), which have been successfully deciphered by genome-guided tools. Moreover, genome metrics supported the split of this genus into (s.s.) and five new other genera. Here, we show that the successful antimicrobial SMs producers belong to s.s. Additionally, we reviewed the occurrence, bioactivities, modes of action, structural, and biosynthetic information of thirty-eight antimicrobial SMs shedding light on their diversity, complexity, and uniqueness as well as the importance of genome-guided strategies to facilitate their discovery. Several NRPS and PKS display unusual features, which are reflected in their structural diversity, important bioactivities, and varied modes of action. Up to now, it is possible to observe a general tendency of SMs being more active against fungi. Although the modes of action and biosynthetic gene clusters of many SMs remain unknown, we highlight the potential of SMs as alternatives to fight against new diseases and antibiotic resistance.

摘要

属于物种非常多样化,不仅在土壤中大量存在,而且还作为植物和动物的共生体或病原体存在。它们复杂的多复制子基因组中含有大量编码抗菌次生代谢物(SMs)的聚酮合酶(PKS)和非核糖体肽合酶(NRPS)基因,这些基因已被基因组导向工具成功破译。此外,基因组指标支持将该属分为(s.s.)和其他五个新属。在这里,我们表明,成功的抗菌 SMs 产生者属于 s.s. 此外,我们回顾了三十八种抗菌 SMs 的发生、生物活性、作用模式、结构和生物合成信息,阐明了它们的多样性、复杂性和独特性,以及基因组导向策略在促进它们的发现方面的重要性。几种 NRPS 和 PKS 表现出不寻常的特征,这反映在它们的结构多样性、重要的生物活性和不同的作用模式上。到目前为止,我们可以观察到 SMs 对真菌的活性更强的一般趋势。尽管许多 SMs 的作用模式和生物合成基因簇仍然未知,但我们强调了 SMs 作为对抗新疾病和抗生素耐药性的替代品的潜力。

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