Premium
A Type I/Type III Polyketide Synthase Hybrid Biosynthetic Pathway for the Structurally Unique ansa Compound Kendomycin
Author(s) -
Wenzel Silke C.,
Bode Helge B.,
Kochems Irene,
Müller Rolf
Publication year - 2008
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.200800456
Subject(s) - polyketide , polyketide synthase , streptomyces coelicolor , gene cluster , streptomyces , biosynthesis , heterologous expression , biology , heterologous , gene , biochemistry , stereochemistry , chemistry , bacteria , genetics , recombinant dna
Kendomycin is a bioactive polyketide that is produced by various Streptomyces strains. It displays strong antibiotic activities against a wide range of bacteria and exhibits remarkable cytotoxic effects on the growth of several human cancer cell lines. In this study we cloned the corresponding biosynthetic locus from the producer Streptomyces violaceoruber (strain 3844‐33C). Our analysis shows that a mixed type I/type III polyketide synthase pathway is responsible for the formation of the fully carbogenic macrocyclic scaffold of kendomycin, which is unprecedented among all of the ansa compounds that have been isolated so far. Heterologous expression of a gene set in Streptomyces coelicolor shows that 3,5‐dihydroxybenzoic acid is an intermediate in the starter unit biosynthesis that is initiated by the type III polyketide synthase. The identification of the kendomycin biosynthetic gene cluster sets the stage to study a novel chain termination mechanism by a type I PKS that leads to carbocycle formation and provides the starting material for the heterologous expression of the entire pathway, and the production of novel derivatives by genetic engineering.