期刊
CHEMBIOCHEM
卷 17, 期 3, 页码 233-238出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201500533
关键词
antibiotics; biosynthesis; methyltransferases; natural products; polyketides
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) [22108003]
- Agricultural Chemical Research Foundation
- Naito Foundation of Japan
- Grants-in-Aid for Scientific Research [22108003] Funding Source: KAKEN
To isolate a key polyketide biosynthetic intermediate for the 16-membered macrolide FD-891 (1), we inactivated two biosynthetic genes coding for post-polyketide synthase (PKS) modification enzymes: a methyltransferase (GfsG) and a cytochrome P450 (GfsF). Consequently, FD-892 (2), which lacks the epoxide moiety at C8-C9, the hydroxy group at C10, and the O-methyl group at O-25 of FD-891, was isolated from the gfsF/gfsG double-knockout mutant. In addition, 25-O-methyl-FD-892 (3) and 25-O-demethyl-FD-891 (4) were isolated from the gfsF and gfsG mutants, respectively. We also confirmed that GfsG efficiently catalyzes the methylation of 2 and 4 in vitro. Further, GfsF catalyzed the epoxidation of the double bond at C8-C9 of 2 and 3 and subsequent hydroxylation at C10, to afford 4 and 1, respectively. These results suggest that a parallel post-PKS modification mechanism is involved in FD-891 biosynthesis.
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