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

该小型企业创新研究(SBIR)第一阶段项目旨在评估海洋生物用于生产多不饱和脂肪酸(PUFA)、二十二碳六烯酸(DHA)的情况。DHA对保持健康很重要，目前全球供应严重短缺。代谢工程将被用来提高天然产生DHA的滨海莫里特氏菌的DHA产量。这将通过删除竞争的代谢途径来增加DHA产生途径的表达来实现。目标是提高产量，使总DHA效价为1.0g/L。这项工作还将为控制中枢代谢流量以及感知和控制脂肪酸含量和产量提供洞察力。因此，这项工作的智力价值延伸到各种新陈代谢产品。该项目的更广泛的影响/商业影响是为DHA开发替代生产系统，DHA是一种可持续和安全的营养食品，目前全球严重供应短缺。数据表明，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病方面发挥着重要作用，如类风湿性关节炎、肥胖症和2型糖尿病。建议普通公众每天至少摄入100-1000毫克多不饱和脂肪酸；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.