Stravidins are peptide antibiotics produced by Streptomyces spp. Their antibacterial activity derives from an unusual amiclenomycin monomer, the warhead that inhibits biotin biosynthesis. Despite being discovered over five decades ago, stravidin biosynthesis has remained a mystery. Using our "metabologenomics" platform, we discover new stravidin analogues and identify the novel biosynthetic machinery responsible for their production. Analysis of the newly identified biosynthetic gene cluster (BGC) indicates the unusual amiclenomycin warhead is derived from chorismic acid, with initial steps similar to those involved in p-amino phenylalanine biosynthesis. However, a distinctive decarboxylation retains the nonaromatic character of a key ring and precedes a one-carbon extension to afford the warhead in its bioactive, untriggered state. Strikingly, we also identified two streptavidin genes flanking the new stravidin BGC reported here. This aligns with the known synergistic activity between the biotin-binding activity of streptavidin and the stravidins to antagonize both biotin biogenesis and bacterial growth.

中文翻译：

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发现了抗生物素蛋白，生物素抗代谢物的生物合成机制。

Stravidins是由链霉菌属（Streptomyces spp）生产的肽抗生素。它们的抗菌活性来自一种不常见的氨苄菌素单体，即抑制生物素生物合成的战斗部。尽管在五十多年前就被发现，但是抗生物素蛋白的生物合成仍然是一个谜。使用我们的“代谢经济学”平台，我们发现了新的抗生物素蛋白类似物，并确定了负责其生产的新型生物合成机制。对新近鉴定的生物合成基因簇（BGC）的分析表明，不常见的amnomynomycin战斗部是从十字花酸衍生而来的，初始步骤类似于对氨基苯丙氨酸生物合成中涉及的步骤。但是，独特的脱羧作用保留了钥匙圈的非芳香族特征，并且在单碳延伸之前使战斗部处于生物活性，未触发状态。令人惊讶的是，我们还鉴定了两个链霉抗生物素蛋白基因，位于此处报道的新链霉抗生物素蛋白BGC的侧面。这与链霉亲和素和stravidins的生物素结合活性之间的已知协同活性一致，以拮抗生物素的生物发生和细菌生长。