Engineering industrial fermentations for renewable amino acid coproducts

描述（由申请人提供）：氨基酸代谢知识对人类健康至关重要，并且具有重要的工业应用。l -赖氨酸是一种具有重要经济和工业意义的必需氨基酸，本研究提出了一种生产l -赖氨酸的副产物方法。如果成功，该研究产生的l -赖氨酸将是红霉素发酵的副产物。目前，l -赖氨酸是由专门的谷氨酸棒状杆菌发酵生产的，因此，与其生产相关的成本不能通过初级发酵产品的生产来吸收。作为红霉素发酵副产物的l -赖氨酸的生产成本将大大降低，而且由于红霉素发酵也是一个非常大规模的过程，因此使用这种方法可以大量生产。此外，本研究还提出了利用不产生红霉素的S. erythraea变体来研究开发一种专门生产l -半胱氨酸的发酵方法的潜力。直到最近，还不需要发酵产生的l -半胱氨酸；但由于最近政府禁止使用动物源性l -半胱氨酸的规定，发酵生产材料的市场显著增长。本研究中使用的模式生物是红霉素生产生物，S. erythraea，一种细菌，已经进行了50多年的密集遗传和生化研究，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：朊病毒疾病，或传染性海绵状脑病（tse），是影响人类和动物的罕见进行性神经退行性疾病家族。朊病毒疾病通常进展迅速，而且总是致命的。这个项目的目的是通过开发一种生产人类使用的氨基酸的生物技术过程，减少在人群中感染TSE<s的风险，这些氨基酸目前是从可能受污染的动物来源获得的。

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.