Discovery and Biosynthesis of Streptosactin, a Sactipeptide with an Alternative Topology Encoded by Commensal Bacteria in the Human Microbiome,Journal of the American Chemical Society

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Discovery and Biosynthesis of Streptosactin, a Sactipeptide with an Alternative Topology Encoded by Commensal Bacteria in the Human Microbiome
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-08-26 , DOI: 10.1021/jacs.0c05546
Leah B Bushin ₁ , Brett C Covington ₁ , Britta E Rued ₂ , Michael J Federle ₂ , Mohammad R Seyedsayamdost _{1,

3}

Affiliation

Mammalian microbiomes encode thousands of biosynthetic gene clusters (BGCs) and represent a new frontier in natural product research. We recently found an abundance of quorum sensing-regulated BGCs in mammalian microbiome streptococci that code for ribosomally synthesized and post-translationally modified peptides (RiPPs) and contain one or more radical S-adenosylmethionine (RaS) enzymes, a versatile superfamily known for catalyzing some of the most unusual reactions in biology. In the current work, we target a wide-spread group of streptococcal RiPP BGCs and elucidate both the reaction carried out by its encoded RaS enzyme and identify its peptide natural product, which we name streptosactin. Streptosactin is the first sactipeptide identified from Streptococcus spp.; it contains two sequential four amino acid sactionine macrocycles, an unusual topology for this compound family. Bioactivity assays reveal potent but narrow-spectrum activity against the producing strain and its closest relatives that carry the same BGC, suggesting streptosactin may be a long-suspected fratricidal agent of Streptococcus thermophilus. Our results highlight mammalian streptococci as a rich source of unusual enzymatic chemistries and bioactive natural products.

中文翻译：

Streptosactin 的发现和生物合成，一种由人类微生物组中的共生细菌编码的具有替代拓扑结构的 Sactipeptide

哺乳动物微生物组编码数以千计的生物合成基因簇 (BGC)，代表了天然产物研究的新前沿。我们最近在哺乳动物微生物群链球菌中发现了大量群体感应调节的 BGC，这些 BGC 编码核糖体合成和翻译后修饰的肽 (RiPP)，并含有一种或多种自由基 S-腺苷甲硫氨酸 (RaS) 酶，这是一种多功能超家族，以催化某些生物学中最不寻常的反应。在当前的工作中，我们针对广泛分布的链球菌 RiPP BGC 组并阐明了由其编码的 RaS 酶进行的反应并鉴定了其肽天然产物，我们将其命名为链球菌素。Streptosactin 是第一个从链球菌属中鉴定出的糖肽；它包含两个连续的四个氨基酸 sactionine 大环，这个复合族的不同寻常的拓扑结构。生物活性测定揭示了对生产菌株及其携带相同 BGC 的近亲的有效但窄谱的活性，表明链球菌素可能是长期怀疑的嗜热链球菌的自相残杀剂。我们的研究结果强调哺乳动物链球菌是不寻常的酶化学和生物活性天然产物的丰富来源。

更新日期：2020-08-26

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