Isolation of hydroxycitric acid-producing Streptomyces sp. U121 and generation of improved mutants by genome shuffling

Abstract

Hydroxycitric acid (HCA) is the principal acid produced by the tropical and subtropical plants Garcinia cambogia and Hibiscus subdariffa. The stereochemistry and biological activities of HCA have been well studied because it is used as a food additive and dietary supplement. Here we review current knowledge on the structure, biological occurrence, physiological activities and microbial production of HCA. Since stereoselective organic synthesis is difficult, and the habitat of the source plants is restricted, the availability of HCA is limited. Hence, we screened microorganisms to supply an alternative source and identified a species of Streptomyces that produces trace amounts of the Hibiscus-type HCA enantiomer. Subsequently, genome shuffling was applied to improve HCA production by the strain. Finally, we obtained improved strains that produce five times more HCA than the parent strain. In combination with a selective screening system, genome shuffling can be used to rapidly improve the production of secondary metabolites by Streptomyces species. Furthermore, genome-wide studies could be used to identify various critical mutations and provide new insights into the cellular regulation of the secondary metabolism of Streptomyces in the near future.