SBIR Phase I: Novel Photosynthetic Biocatalysts for Synthesis of Malic Acid

SBIR 第一阶段：用于合成苹果酸的新型光合生物催化剂

• 批准号: 1215144
• 负责人: Abhay Singh
• 金额: $ 15万
• 依托单位: MOgene Green Chemicals LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1215144&HistoricalAwards=false
• 关键词: SBIR; Phase; Novel; Photosynthetic; Biocatalysts

This Small Business Innovation Research Phase I project aims to engineer novel biocatalysts for cost-effective production of malic acid from CO2. Malic acid is a key intermediate in energy metabolism of all living species. Additionally, presence of two carboxyl and one hydroxyl groups makes it an important building block for production of diverse chemicals and chemical intermediates. Attempts to engineer heterotrophic biocatalysts for production of malic acid have had limited success due to the inherent limitations of accessing the substrate required for the key biosynthetic enzyme. We have developed an innovative strategy to co-localize this key enzyme within carboxysomes naturally found in photosynthetic microorganisms. Carboxysomes are leveraged by ribulose-1,5-bisphosphate carboxylase/oxygenase to overcome their kinetic deficiency for CO2, a cosubstrate. The engineered metabolic pathway will allow conversion of 3- phosphoglycerate naturally produced inside carboxysome to malic acid. The anticipated result of this SBIR Phase 1 research project is establishment of a groundbreaking and cost-effective technology that will convert CO2 into malic acid using energy derive from sunlight. The Broader/Commercial outcome of the proposed research will be to offer multiple benefits and applications: 1) Development of an efficient biocatalyst that could significantly reduce the production cost of malic acid. Lower production cost and presence of multiple functional groups will open new market opportunities. 2) Production of enantiomerically pure L-malic acid from renewable feedstock, a preferred additive for food and pharmaceutical applications over the racemic mixtures produced by the chemical method. 3) An attractive and immediate opportunity to reduce carbon footprint of the existing biofuel industries. 4) Opportunity to target other CO2 utilizing enzymes to this locale within cells and to use CO2 more efficiently in making other important biomolecules thus opening new commercial possibilities. 5) Finally, it will open up the opportunity to link light harvesting more effectively to carbon fixation since enzymes that make malic acid have substantially higher turnover capability than RuBisCO. Success of the proposed process technology will contribute to the economic and energy security of the U.S. by reducing the dependence on fossil fuels and emission of greenhouse gas emission, and use of CO2 in the chemical industry instead of being an emitter.

该小企业创新研究第一阶段项目旨在设计新型生物催化剂，以经济高效地利用二氧化碳生产苹果酸。苹果酸是所有生物物种能量代谢的关键中间体。此外，两个羧基和一个羟基的存在使其成为生产各种化学品和化学中间体的重要组成部分。由于获取关键生物合成酶所需底物的固有限制，设计用于生产苹果酸的异养生物催化剂的尝试取得了有限的成功。我们开发了一种创新策略，将这种关键酶共定位于光合微生物中天然存在的羧基体中。 1,5-二磷酸核酮糖羧化酶/加氧酶利用羧基体来克服其对 CO2（共底物）的动力学缺陷。工程代谢途径将允许羧基体内自然产生的 3-磷酸甘油酸转化为苹果酸。 SBIR 第一阶段研究项目的预期结果是建立一项突破性且具有成本效益的技术，利用来自阳光的能量将二氧化碳转化为苹果酸。拟议研究的更广泛/商业成果将提供多种好处和应用：1）开发一种有效的生物催化剂，可以显着降低苹果酸的生产成本。较低的生产成本和多个功能组的存在将开辟新的市场机会。 2) 用可再生原料生产对映体纯的 L-苹果酸，与化学方法生产的外消旋混合物相比，它是食品和制药应用的首选添加剂。 3) 减少现有生物燃料行业碳足迹的一个有吸引力且直接的机会。 4) 有机会将其他利用二氧化碳的酶定位到细胞内的这一区域，并更有效地利用二氧化碳来制造其他重要的生物分子，从而开辟新的商业可能性。 5) 最后，它将提供将光捕获与碳固定更有效地联系起来的机会，因为制造苹果酸的酶比 RuBisCO 具有更高的周转能力。该工艺技术的成功将减少对化石燃料的依赖和温室气体排放，并在化学工业中使用二氧化碳而不是排放者，从而为美国的经济和能源安全做出贡献。