A head-to-head comparison of eneamide and epoxyamide inhibitors of glucosamine-6-phosphate synthase from the dapdiamide biosynthetic pathway.
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ABSTRACT:
SUBMITTER: Hollenhorst MA
PROVIDER: S-EPMC3097904 | biostudies-literature | 2011 May
REPOSITORIES: biostudies-literature
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A head-to-head comparison of eneamide and epoxyamide inhibitors of glucosamine-6-phosphate synthase from the dapdiamide biosynthetic pathway.
Hollenhorst Marie A MA Ntai Ioanna I Badet Bernard B Kelleher Neil L NL Walsh Christopher T CT
Biochemistry 20110426 19
The dapdiamides make up a family of antibiotics that have been presumed to be cleaved in the target cell to enzyme-inhibitory N-acyl-2,3-diaminopropionate (DAP) warheads containing two alternative electrophilic moieties. Our prior biosynthetic studies revealed that an eneamide warhead is made first and converted to an epoxyamide via a three-enzyme branch pathway. Here we provide a rationale for this logic. We report that the R,R-epoxyamide warhead is a more efficient covalent inactivator of gluc ...[more]
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