Engineering industrial fermentations for renewable amino acid coproducts

描述(申请人提供)：氨基酸新陈代谢知识对人类健康至关重要，也有重要的工业应用。本研究建议开发一种联产方法来生产L赖氨酸，这是一种具有重要经济和工业意义的必需氨基酸。如果成功，本研究生产的L赖氨酸将是红霉素发酵的副产品。目前，L赖氨酸是由谷氨酸棒状杆菌专用发酵生产的，因此，与其生产相关的成本无法通过生产一次发酵产品来吸收。作为红霉素发酵的副产物生产的L赖氨酸的生产成本将大大降低，并且可以使用这种方法大量生产，因为红霉素发酵也是一个非常大规模的过程。此外，这项研究还建议开发一种专门用于L半胱氨酸生产的发酵方法的可能性，该方法使用一种不产生红霉素的红链霉菌变种。直到最近，发酵生产的L半胱氨酸还没有必要；但由于最近政府出台了禁止使用动物源性L半胱氨酸的规定，发酵生产的材料的市场已经显著增长。这项研究中使用的模式生物是红霉素产生生物红霉菌，这是一种细菌，50多年来一直是密集的遗传和生化研究的主题，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：Pron病，或可传播的海绵状脑病(TSE)，是一种罕见的进行性神经退行性疾病家族，对人类和动物都有影响。Pron疾病通常进展迅速，而且总是致命的。该项目旨在通过开发生产人类使用的氨基酸的生物技术过程来降低在人群中感染谢霆锋S的风险，目前氨基酸是从可能受到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.