Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, United States.
ACS Chem Biol. 2020 May 15;15(5):1134-1140. doi: 10.1021/acschembio.9b00890. Epub 2020 Jan 9.
Stravidins are peptide antibiotics produced by 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 -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.
斯特拉丁是由 spp. 产生的肽类抗生素。它们的抗菌活性源自一种不寻常的amiclenomycin 单体，即抑制生物素生物合成的弹头。尽管斯特拉丁的生物合成在五十年前就被发现了，但它仍然是一个谜。我们使用“代谢基因组学”平台发现了新的斯特拉丁类似物，并确定了负责其产生的新型生物合成机制。对新鉴定的生物合成基因簇 (BGC) 的分析表明，不寻常的amiclenomycin 弹头是由支链酸衍生而来的，其最初步骤与涉及 -氨基苯丙氨酸生物合成的步骤相似。然而，一个独特的脱羧作用保留了一个关键环的非芳族特征，并在一个碳原子的延伸之前，使弹头处于其生物活性、未触发的状态。引人注目的是，我们还在新报道的斯特拉丁 BGC 两侧鉴定出了两个链霉亲和素基因。这与链霉亲和素的生物素结合活性与斯特拉丁协同拮抗生物素生物合成和细菌生长的已知协同活性一致。
