Generation of incednine derivatives by mutasynthesis
Akimasa Miyanaga1, Ryoma Takaku1, Makoto Takaishi1
1Department of Chemistry, Tokyo Institute of Technology, 2-12-1 Meguro-ku, O-okayama, Tokyo, 152-8551, Japan.
Abstract:
The macrolactam antibiotic incednine, isolated from Streptomyces sp. ML694-90F3, contains a (S)-3-aminobutyric acid moiety in its polyketide aglycon. In this study, we performed mutasynthesis to generate incednine derivatives. We successfully obtained 28-methylincednine by feeding 3-aminopentanoic acid into culture of a strain in which the glutamate 2,3-aminomutase gene idnL4, whose product is responsible for supplying 3-aminobutyric acid, was disrupted. 28-Methylincednine showed similar suppressive activity of the antiapoptotic function of oncoprotein Bcl-xL to that of incednine. Thus, this study highlights the applicability of the mutasynthesis approach in generation of novel β-amino acid-containing macrolactam polyketide derivatives.
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