Department of Molecular Sciences, Macquarie University, NSW 2109, Australia.
Microbial Screening Technologies, Smithfield, NSW 2164, Australia.
Org Biomol Chem. 2021 Jul 21;19(27):6147-6159. doi: 10.1039/d1ob00600b. Epub 2021 Jun 28.
LCMS-guided screening of a library of biosynthetically talented bacteria and fungi identified Streptomyces sp. MST- as a prolific producer of chlorinated metabolites. We isolated and characterised six new and nine reported compounds from MST-, belonging to three discrete classes - the depsipeptide svetamycins, the indolocarbazole borregomycins and the aromatic polyketide anthrabenzoxocinones. Following genome sequencing of MST-, we describe, for the first time, the svetamycin biosynthetic gene cluster (sve), its mosaic structure and its relationship to several distantly related gene clusters. Our analysis of the sve cluster suggested that the reported stereostructures of the svetamycins may be incorrect. This was confirmed by single-crystal X-ray diffraction analysis, allowing us to formally revise the absolute configurations of svetamycins A-G. We also show that the borregomycins and anthrabenzoxocinones are encoded by a single supercluster (bab) implicating superclusters as potential nucleation points for the evolution of biosynthetic gene clusters. These clusters highlight how individual enzymes and functional subclusters can be co-opted during the formation of biosynthetic gene clusters, providing a rare insight into the poorly understood mechanisms underpinning the evolution of chemical diversity.
LCMS 引导的生物合成有才华的细菌和真菌文库筛选鉴定出链霉菌 MST- 是氯化代谢产物的丰富生产者。我们从 MST- 中分离和鉴定了六种新的和九种已报道的化合物，它们属于三个不同的类别 - 去肽肽 Svetamycins、吲哚咔唑 Borregomycins 和芳香聚酮 Anthrabenzoxocinones。在对 MST- 进行基因组测序后，我们首次描述了 Svetamycin 生物合成基因簇（sve），其马赛克结构及其与几个远缘基因簇的关系。我们对 sve 簇的分析表明，报道的 Svetamycins 立体结构可能不正确。这通过单晶 X 射线衍射分析得到了证实，使我们能够正式修正 Svetamycins A-G 的绝对构型。我们还表明，Borregomycins 和 Anthrabenzoxocinones 由单个超级簇（bab）编码，这暗示超级簇可能是生物合成基因簇进化的起始点。这些簇突出了单个酶和功能亚簇如何在生物合成基因簇的形成过程中被共同利用，为理解化学多样性进化的潜在机制提供了罕见的见解。
