Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 131, Issue 44, Pages 16033-+Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja9071578
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Funding
- NIH [CA 108874]
- Hans W. Vahlteich Professorship
- Rackham Predoctoral Fellowship
- NSF Career [CHE-05-47699]
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Biosynthetic innovation in natural product systems is driven by the recruitment of new genes and enzymes into these complex pathways. Here, an unprecedented decarboxylative chain termination mechanism is described for the polyketide synthase of curacin A, an anticancer lead compound isolated from the marine cyanobacterium Lyngbya majuscula. The unusual chain termination module containing adjacent sulfotransferase (ST) and thioesterase (TE) catalytic domains embedded in CurM was biochemically characterized. The TE was proved to catalyze a hydrolytic chain release of the polyketide chain elongation intermediate. Moreover, a selective ST-mediated sulfonation of the (R)-beta-hydroxyl group was found to precede TE-mediated hydrolysis, triggering a successive decarboxylative elimination and resulting in the formation of a rare terminal olefin in the final metabolite.
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