SBIR Phase I: Metabolic Engineering of Moritella marina MP-1 for DHA Production

这项小型企业创新研究（SBIR）第一阶段项目旨在评估利用海洋生物生产多不饱和脂肪酸（PUFA），二十二碳六烯酸（DHA）。DHA对保持身体健康很重要，在世界范围内供应严重短缺。代谢工程将用于增加天然产生DHA的滨海森氏菌的DHA产量。这将通过删除竞争性代谢途径来增加dha产生途径的表达来实现。目标是提高产量，使总DHA滴度达到1.0 g/L。这项工作还将为中央代谢通量的控制以及脂肪酸含量和生产的感知和控制提供见解。因此，这项工作的知识价值延伸到各种代谢产物。该项目的更广泛影响/商业影响是开发DHA的替代生产系统，DHA是一种可持续和安全的营养保健品，在全球范围内严重供应短缺。数据显示，omega-3脂肪酸，如DHA，在促进心脏健康、大脑健康、儿童和婴儿发育以及预防各种慢性疾病（如类风湿关节炎、肥胖和2型糖尿病）方面发挥着重要作用。建议公众每天摄入至少100-1000毫克的PUFA；目前DHA的主要来源是冷水鱼，无法满足全球需求。商业目标是生物制造DHA，然后向营养补充剂和食品制造商销售富含DHA的油，以满足对该产品日益增长的需求。

This Small Business Innovation Research (SBIR) Phase I project aims to evaluate the use of a marine organism for production of the polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA). DHA is important for maintaining good health and is in serious supply shortage worldwide. Metabolic engineering will be used to increase DHA production in Moritella marina, which naturally produces DHA. This will be accomplished by deletion of competing metabolic pathways to increase expression of the DHA-producing pathway. The goal is to increase production such that the overall DHA titer is 1.0 g/L. This work also will provide insight into control of central metabolic flux and sensing and control of fatty acid content and production. Thus, the intellectual merit of this work extends to a variety of metabolic products. The broader impact/commercial impact of this project is the development of an alternative production system for DHA, a sustainable and safe nutraceutical that is in serious supply shortage worldwide. Data suggest that omega-3 fatty acids, such as DHA, play important roles in enhancing heart health, brain health, child and infant development and preventing various chronic diseases, such as rheumatoid arthritis, obesity and type-2 diabetes. It is recommended that the general public consume at least 100-1000 mg of PUFA daily; the current primary source for DHA is from cold water fish, which cannot meet global demand. The commercial goal is to biomanufacture DHA, and then market a DHA-enriched oil to nutritional supplement and food manufacturers to meet the growing demand for this product.