期刊
ACS CHEMICAL BIOLOGY
卷 15, 期 5, 页码 1134-1140出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.9b00890
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资金
- National Center for Complementary and Integrative Health (NCCIH) of the National Institutes of Health [R01AT009143]
- National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) [F32GM122397]
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 onecarbon 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.
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