Parallel Post-Polyketide Synthase Modification Mechanism Involved in FD-891 Biosynthesis in Streptomyces graminofaciens A-8890.
Chembiochem
; 17(3): 233-8, 2016 Feb 02.
Article
em En
| MEDLINE
| ID: mdl-26630077
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.
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MEDLINE
Assunto principal:
Streptomyces
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Macrolídeos
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Policetídeo Sintases
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article