Journal
CHEMBIOCHEM
Volume 9, Issue 10, Pages 1609-1616Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200700635
Keywords
biosynthesis; natural products; pikromycin; polyketides; triketides
Funding
- NIGMS NIH HHS [R01 GM076477, R01 GM076477-03, R01 GM076477-04, R01 GM0876477] Funding Source: Medline
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The pikromycin polyketide synthase (PKS) of S. venezuelae, which consists of one loading module and six extension modules, is responsible for the formation of the hexaketide narbonolide, a key intermediate in the biosynthesis of the antibiotic pikromycin. S. venezuelae strains in which PikAl, which houses the loading domain and first two modules of the PKS, is either absent or catolytically inactive, produce no. pikromycin product. When these strains ore grown in the presence of a synthetically prepared triketide product, activated as the N-acetylcysteamine thioester, pikromycin yields are restored to as much as 11% of that seen in the wild-type strain. Feeding analogues of the triketide intermediate provides pikromycin analogues bearing different alkyl substituents at C13 and C14. One of these analogues, Delta(15,16)-dehydro-pikromycin, exhibits improved antimicrobial activity relative to pikromycin.
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