Abstract

Cyclodipeptide synthases (CDPSs) are a recently described family of enzymes that employ aminoacyl charged tRNAs in the biosynthesis of diketopiperazines. Fewer than a dozen CDPSs have been characterized to date. Bioinformatics analysis revealed two putative CDPSs in the genome of a marine actinomycete, Nocardiopsis sp. (CMB-M0232). These CDPSs were cloned and expressed in E. coli. Chemical extracts from these recombinant E. coli were analyzed by LC/MS, revealing both CDPSs catalyze production of cyclodipeptides including cyclo (L-Trp-L-Trp). These CDPSs are putative enzymes in biosynthesis of nocardioazine A, a prenylated anticancer diketopiperazine.

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