Novel industrial bioprocesses for production of key valuable steroid precursors from phytosterols

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Steroids are specific structure terpenoid lipids that occur widely in living systems. Over 250 sterols and related compoundshave been reported in plants, insects, vertebrates and lower eukaryotes such as yeasts. Steroid hormones control cellproliferation and tissue differentiation and modulate gene expression. Hence, steroid based pharmaceuticals are importantfor human and animal health in; (a) disease prevention (antitumor, anti-estrogenic); (b) disease therapy (cancer, obesity)and (c) life-style choices (menopause, human fertility). As a result, about 300 approved steroid drugs exist to date and thenumbers are growing. Indeed the market for steroid drugs lies second only to that for antibiotics; the global market forsteroids is in excess of US $10 billion and more than 1,000,000 tons annually. In recent years the conversion ofagricultural, food or cellulose industrial wastes containing phytosterols into high value steroid compounds has become ahighly attractive goal. However studies to date indicate that improvements are needed in phytosterol culture broth solubility,microbial strains, and product recovery. Project MySterI will focus on improvement of the known bioconverting bacterium,Mycobacterium sp. NRRL B-3085, to replace the existing microbial/chemical multistep processes with single-stepproduction processes for androst-4-ene-3,17-dione (AD) (intermediary precursor), 11alpha hydroxyandrost-4-ene-3,17-dione (11-alpha-OH-AD), 3beta-hydroxyandrost-5-ene-17-one (DHEA) or testosterone from phytosterols. The use of singlestepbioconversion processes will reduce costs and loss of yield associated with the multistep processes, and will beenvironmentally cleaner. The MySterI pipeline includes the development of genetic engineering tools, strain improvementsupported by 'omics information, scale down and up process and simplified product recovery, all of which comprise acomplete improvement of the production process.