TY - JOUR
T1 - Generation of novel pikromycin antibiotic products through mutasynthesis
AU - Gupta, Shuchi
AU - Lakshmanan, Venkatraman
AU - Kim, Beom Seok
AU - Fecik, Robert
AU - Reynolds, Kevin A.
PY - 2008/7/2
Y1 - 2008/7/2
N2 - 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 PikAI, which houses the loading domain and first two modules of the PKS, is either absent or catalytically inactive, produce no pikromycin product. When these strains are 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, Δ15,16-dehydropikromycin, exhibits improved antimicrobial activity relative to pikromycin.
AB - 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 PikAI, which houses the loading domain and first two modules of the PKS, is either absent or catalytically inactive, produce no pikromycin product. When these strains are 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, Δ15,16-dehydropikromycin, exhibits improved antimicrobial activity relative to pikromycin.
KW - Biosynthesis
KW - Natural products
KW - Pikromycin
KW - Polyketides
KW - Triketides
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U2 - 10.1002/cbic.200700635
DO - 10.1002/cbic.200700635
M3 - Article
C2 - 18512859
AN - SCOPUS:48649086914
SN - 1439-4227
VL - 9
SP - 1609
EP - 1616
JO - ChemBioChem
JF - ChemBioChem
IS - 10
ER -