Journal
BIOCHEMISTRY
Volume 58, Issue 25, Pages 2804-2808Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biochem.9b00379
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Funding
- Duke University Medical Center
- National Institute of General Medical Sciences [R01 GM112838]
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Mitomycins make up a group of antitumor natural products that are biosynthesized from amino-hydroxybenzoic acid (AHBA) and N-acetylglucosamine (GlcNAc). While the biosynthetic gene cluster was reported two decades ago, the mechanism by which the two building blocks, AHBA and GlcNAc, are coupled during biosynthesis remained uncharacterized. Here we report evidence that AHBA is first loaded onto an MmcB acyl carrier protein (ACP) by a MitE acyl ACP synthetase, followed by a transfer of GlcNAc from UDP-GlcNAc by MitB. The results suggest that the early steps of mitomycin biosynthesis proceed via intermediates linked to MmcB.
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