ABSTRACTNatural products produced by microorganisms are important starting compounds for drug discovery. Secondary metabolites, including antibiotics, have been isolated from differentStreptomycesspecies. The production of these metabolites depends on the culture conditions. Therefore, the development of a new culture method can facilitate the discovery of new natural products. Here, we show that mycolic acid-containing bacteria can influence the biosynthesis of cryptic natural products inStreptomycesspecies. The production of red pigment byStreptomyces lividansTK23 was induced by coculture withTsukamurella pulmonisTP-B0596, which is a mycolic acid-containing bacterium. Only living cells induced this pigment production, which was not mediated by any substances.T.pulmoniscould induce natural-product synthesis in otherStreptomycesstrains too: it altered natural-product biosynthesis in 88.4% of theStreptomycesstrains isolated from soil. The other mycolic acid-containing bacteria,Rhodococcus erythropolisandCorynebacterium glutamicum, altered biosynthesis in 87.5 and 90.2% of theStreptomycesstrains, respectively. The coculture broth ofT.pulmonisandStreptomyces endusS-522 contained a novel antibiotic, which we named alchivemycin A. We concluded that the mycolic acid localized in the outer cell layer of the inducer bacterium influences secondary metabolism inStreptomyces, and this activity is a result of the direct interaction between the mycolic acid-containing bacteria andStreptomyces. We used these results to develop a new coculture method, called the combined-culture method, which facilitates the screening of natural products.
The International Conference of Natural Product Biosynthesis (ICNPB, 8th US–Japan seminar on the Biosynthesis of Natural Products)
