Engineering industrial fermentations for renewable amino acid coproducts

描述（由申请人提供）：氨基酸代谢的知识对人类健康至关重要，也具有重要的工业应用。本研究提出了一种生产L-赖氨酸的联产方法，L-赖氨酸是一种具有重要经济和工业意义的必需氨基酸。如果成功，本研究产生的L-赖氨酸将是使用红多孢菌发酵红霉素的副产物。目前，L-赖氨酸由专用的谷氨酸棒杆菌发酵生产，因此，具有与其生产相关的成本，这些成本不能通过初级发酵产物的生产来吸收。从红霉素发酵中作为副产物产生的L-赖氨酸的生产成本将大大降低，并且由于红霉素发酵也是一种非常大规模的方法，因此使用该方法可以大量生产。此外，本研究还提出了开发一种专用的发酵方法生产L-半胱氨酸的潜力，使用红霉素非生产变异的S。菜直到最近，还不需要发酵生产的L-半胱氨酸;但由于最近政府规定禁止使用动物来源的L-半胱氨酸，发酵生产材料的市场已经显着增长。本研究中使用的模式生物是红霉素产生菌S.该细菌是50多年来深入的遗传和生物化学研究的对象，为建立氨基酸生产的商业过程提供了坚实的基础。公共卫生相关性：朊病毒病，或传染性海绵状脑病（TSE），是一个家庭的罕见的进行性神经退行性疾病，影响人类和动物。朊病毒疾病通常进展迅速，并且总是致命的。该项目旨在通过开发用于生产人类使用的氨基酸的生物技术工艺来降低人群中获得TSE<s的风险，目前这些氨基酸来自可能受污染的动物来源。

DESCRIPTION (provided by applicant): Knowledge of amino acid metabolism is critical to human health and has significant industrial applications as well. This study proposes to develop a coproduct method for the production of L-lysine, an essential amino acid of great economic and industrial importance. If successful, the L-lysine produced as a result of this study will be a coproduct of the erythromycin fermentation using Saccharopolyspora erythraea. Currently, L-lysine is produced from dedicated Corynebactium glutamicum fermentations, and as such, has costs associated with its production that are not absorbed through the production of a primary fermentation product. L-lysine produced as a coproduct from the erythromycin fermentation would be substantially less expensive to produce, and large quantities could be produced using this method because the erythromycin fermentation is also a very large-scale process. In addition, this study also proposes to investigate the potential for developing a dedicated fermentation method for L-cysteine production, using an erythromycin non-producing variant of S. erythraea. Until recently there was no need for fermentation-produced L-cysteine; but due to recent government regulations against the use of animal derived L-cysteine, the market for fermentation-produced material has grown significantly. The model organism used in this study is the erythromycin producing organism, S. erythraea, a bacterium that has been the subject of over 50 years of intensive genetic and biochemical research, providing a solid foundation upon which to build commercial processes for amino acid production. Public Health Relevance: Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a family of rare progressive neurodegenerative disorders that affect both humans and animals. Prion diseases are usually rapidly progressive and always fatal. This project aims to reduce the risk of acquiring TSE<s in the population through the development of a biotechnological process for the production of amino acids that are used by humans and are currently obtained from possibly contaminated animal sources.