Parallel Post‐Polyketide Synthase Modification Mechanism Involved in FD‐891 Biosynthesis in Streptomyces graminofaciens A‐8890 |
| |
| Authors: | Prof. Dr. Fumitaka Kudo Koichi Kawamura Takashi Furuya Hiroto Yamanishi Atsushi Motegi Akiko Komatsubara Mario Numakura Prof. Dr. Akimasa Miyanaga Prof. Dr. Tadashi Eguchi |
| |
| Affiliation: | 1. Department of Chemistry, Tokyo Institute of Technology, Meguro-ku, Tokyo, Japan;2. Department of Chemistry and Materials Science, Tokyo Institute of Technology, Meguro-ku, Tokyo, Japan |
| |
| Abstract: | 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. |
| |
| Keywords: | antibiotics biosynthesis methyltransferases natural products polyketides |
|
|
