Monday, July 30, 2007
P88
Engineering of novel phoslactomycins from precursor-directed biosynthesis
Nadaraj Palaniappan, Mamoun Alhamadsheh, and Kevin Reynolds. Department of Chemistry, Portland State University, 1719 SW 10th Ave, SB2, Room 262, Portland, OR 97201
The phoslactomycins (PLMs) A-F are a family of potent antifungal and antitumor antibiotics, biosynthesized by Streptomyces sp HK 803 using a cyclohexanecarboxylic acid (CHC) as starter unit. Recently we reported the PLM biosynthetic gene cluster that includes the complete set of biosynthesis genes for the CHC-CoA starter units. By PCR targeting technology, the chcA gene of CHC-CoA biosynthesis pathway of the wild type and PLM B producing NP2 mutant strains were blocked and the newly generated mutants lacked the ability to produce PLMs. Supplementation of various exogenous carboxylic acids both in liquid and solid fermentation conditions led to successful incorporation of these elements to produce more than 30 PLM analogs. In this presentation, we will report the characterization, structural analysis, and biological properties of some the selected novel PLM analogs engineered by the precursor-directed biosynthesis approach.
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See more of The Annual Meeting and Exhibition 2007 (July 29 - August 2, 2007)