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

甾体化合物是一类结构特殊的萜类脂质，广泛存在于生命系统中。在植物、昆虫、脊椎动物和酵母等低等真核生物中发现了250多种甾醇及其相关化合物。类固醇激素控制细胞增殖和组织分化，并调节基因表达。因此，基于类固醇的药物在以下方面对人类和动物健康是重要的：（a）疾病预防（抗肿瘤、抗雌激素）;（B）疾病治疗（癌症、肥胖）和（c）生活方式选择（绝经、人类生育）。因此，到目前为止，大约有300种批准的类固醇药物存在，并且正在增长。实际上，类固醇药物的市场仅次于抗生素;全球类固醇药物市场超过100亿美元，每年超过100万吨。近年来，将含有植物甾醇的农业、食品或纤维素工业废弃物转化为高价值的甾体化合物已成为一个极具吸引力的目标。然而，迄今为止的研究表明，需要改进植物甾醇培养液的溶解度，微生物菌株和产品回收。MySterI项目将专注于改进已知的生物转化细菌，分枝杆菌属NRRL B-3085，用雄甾-4-烯-3，17-二酮（AD）的单步生产工艺取代现有的微生物/化学多步工艺（中间前体）、11 α-羟基雄甾-4-烯-3，17-二酮（11-α-OH-AD）、3 β-羟基雄甾-5-烯-17-酮（DHEA）或来自植物甾醇的睾酮。使用单步生物转化工艺将降低成本和与多步工艺相关的产量损失，并将使环境更清洁。MySterI管道包括基因工程工具的开发、由组学信息支持的菌株改良、规模缩小和扩大工艺以及简化的产品回收，所有这些都包括生产工艺的完整改进。

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.