Comparative Genomic and Metabolic Analysis of Streptomyces sp. RB110 Morphotypes Illuminates Genomic Rearrangements and Formation of a New 46-Membered Antimicrobial Macrolide,ACS Chemical Biology

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Comparative Genomic and Metabolic Analysis of Streptomyces sp. RB110 Morphotypes Illuminates Genomic Rearrangements and Formation of a New 46-Membered Antimicrobial Macrolide
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2021-07-17 , DOI: 10.1021/acschembio.1c00357
Soohyun Um ₁ , Huijuan Guo ₁ , Sirinthra Thiengmag ₂ , René Benndorf ₁ , Robert Murphy ₃ , Maja Rischer ₁ , Daniel Braga ₂ , Michael Poulsen ₃ , Z Wilhelm de Beer ₄ , Gerald Lackner ₂ , Christine Beemelmanns ₁

Affiliation

Morphotype switches frequently occur in Actinobacteria and are often associated with disparate natural product production. Here, we report on differences in the secondary metabolomes of two morphotypes of a Streptomyces species, including the discovery of a novel antimicrobial glycosylated macrolide, which we named termidomycin A. While exhibiting an unusual 46-member polyene backbone, termidomycin A (1) shares structural features with the clinically important antifungal agents amphotericin B and nystatin A1. Genomic analyses revealed a biosynthetic gene cluster encoding for a putative giant type I polyketide synthase (PKS), whose domain structure allowed us to propose the relative configuration of the 46-member macrolide. The architecture of the biosynthetic gene cluster was different in both morphotypes, thus leading to diversification of the product spectrum. Given the high frequency of genomic rearrangements in Streptomycetes, the metabolic analysis of distinct morphotypes as exemplified in this study is a promising approach for the discovery of bioactive natural products and pathways of diversification.

中文翻译：

链霉菌属的比较基因组和代谢分析。RB110 形态型揭示基因组重排和新的 46 成员抗菌大环内酯的形成

形态转换经常发生在放线菌中，并且通常与不同的天然产物生产有关。在这里，我们报告了链霉菌的两种形态型的次级代谢组的差异物种，包括发现了一种新型抗菌糖基化大环内酯，我们将其命名为 termidomycin A。 termidomycin A (1) 具有不寻常的 46 成员多烯骨架，但与临床上重要的抗真菌剂两性霉素 B 和制霉菌素 A1 具有相同的结构特征。基因组分析揭示了一个编码假定的巨型 I 型聚酮化合物合酶 (PKS) 的生物合成基因簇，其结构域结构使我们能够提出 46 成员大环内酯的相对构型。两种形态型的生物合成基因簇的结构不同，从而导致产品谱的多样化。鉴于链霉菌中基因组重排的频率很高，

更新日期：2021-08-20

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