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  • Title: Sponge-derived Streptomyces producing isoprenoids via the mevalonate pathway.
    Author: Izumikawa M, Khan ST, Takagi M, Shin-ya K.
    Journal: J Nat Prod; 2010 Feb 26; 73(2):208-12. PubMed ID: 20085309.
    Abstract:
    In the course of our screening program for isoprenoids of marine actinobacterial origin, 523 actinobacterial strains were isolated from marine samples. Actinobacteria usually use the 2-C-methyl-d-erythritol 4-phosphate pathway for the production of primary metabolites, but some have been reported to use the mevalonate (MVA) pathway for the production of isoprenoids as secondary metabolites. 3-Hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) is a key enzyme and plays an important role in the MVA pathway. Therefore, we screened strains possessing the HMGR gene from the 523 strains mentioned above and also investigated isoprenoid compounds from cultures of strains possessing HMGR genes. As a result, Streptomyces sp. SpC080624SC-11 isolated from a marine sponge, Cinachyra sp., was shown to possess the HMGR gene and produce novel isoprenoids, JBIR-46 (1), -47 (2), and -48 (3). On the basis of extensive NMR and MS analyses, the structures of 1-3 were determined to be phenazine derivatives harboring dimethylallyl moieties. Furthermore, the isoprene units of 2 and 3 were confirmed to be synthesized via the MVA pathway in a feeding experiment using [1-(13)C]acetate.
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