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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Post-PKS Tailoring of Phoslactomycins Involving Two Cytochrome P450s
Hengyu Li1, Miao Sun1, Juan Zhao2
1School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
None:
Combining in vivo and in vitro approaches, we elucidated the phoslactomycin post-PKS tailoring pathway in S. platensis. Gene inactivation of pnT1-pnT7 revealed seven phoslactomycin derivatives (four novel). Two cytochrome P450s were identified: PnT3 (mediating dual-site, multistep C-8/C-25 oxidation) and PnT7 (catalyzing C-18 hydroxylation). Activity evaluation established essential C-9 phosphate and detrimental ε-lactone/C-3 malonyl effects. These findings bridge the gap in phoslactomycin modification, highlighting a versatile P450 PnT3, and provide SAR foundations for PP2A inhibitor design.
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