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Parallel Post‐Polyketide Synthase Modification Mechanism Involved in FD‐891 Biosynthesis in Streptomyces graminofaciens A‐8890
Author(s) -
Kudo Fumitaka,
Kawamura Koichi,
Furuya Takashi,
Yamanishi Hiroto,
Motegi Atsushi,
Komatsubara Akiko,
Numakura Mario,
Miyanaga Akimasa,
Eguchi Tadashi
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500533
Subject(s) - polyketide , polyketide synthase , biosynthesis , stereochemistry , hydroxylation , methyltransferase , moiety , mutant , chemistry , enzyme , streptomyces , methylation , cytochrome p450 , demethylation , atp synthase , biochemistry , biology , gene , bacteria , genetics , dna methylation , gene expression
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.