SusChEM: Enhancing Tolerance and Performance of a Renewable Aromatic Biorefinery

[1511637]尼尔森，大卫，虽然微生物可以被改造成将可再生生物质转化为一系列有用的化学物质，但同样的产物往往会抑制生产微生物的生产力。该项目旨在探索为支持增强的化学品生产而设计更具耐受性的微生物的策略。将首先设计新的酶途径，使目前从石油中提取的四种芳香产品的个体生物合成成为可能。他们的替代性生物生产将最终帮助美国减少对外国石油和天然气的依赖。该项目开发的材料和策略最终将不仅有利于可再生芳香化学品的生产，而且有利于广泛的其他有用的生物产品，包括生物燃料。除了通过创建酶途径来扩大微生物合成的传统石化替代品的数量和多样性外，该项目还进一步寻求探索设计更具耐受性的微生物的策略，以支持提高化学品生产。将首先设计新的酶途径，以实现四种芳香产物的单独生物合成：苯乙烯，(S)-苯乙烯氧化物，(R)-苯乙烯乙二醇和2-苯乙醇。为了对抗与微生物化学生产相关的抑制效应，将探索通过在细胞合成时主动排出有毒产物来提高耐受性和生产力的策略。这将在原生和异种外排转运蛋白的帮助下实现。最后，新的基因回路将被设计成仅在细胞需要时控制外排泵的表达，从而允许细胞为进一步的化学生产保留宝贵的资源。新型芳香诱导基因回路控制转运体表达的发展，将证明自我驱动控制策略如何通过为细胞提供感知和响应环境和内在代谢动态变化的能力，来维持最大的宿主适应性。将研究与教育和外联活动紧密结合将是这个项目的关键组成部分。该奖项由CBET部门的生物技术和生化工程项目颁发，由分子和细胞生物学部门的系统和合成生物学项目共同资助。

1511637 Nielsen, David Although microorganisms can be engineered to convert renewable biomass into an array of useful chemicals, the same products often inhibit the productivity of the producing microbes. This project seeks to explore strategies for engineering more tolerant microbes in support of enhanced chemical production. Novel enzyme pathways will first be engineered to enable the individual biosynthesis of four aromatic products that are currently derived from petroleum. Their alternative bioproduction will ultimately help to reduce U.S. dependence on foreign oil and gas. The materials and strategies developed in this project will ultimately benefit not only the production of renewable aromatic chemicals, but also a broad range of other useful bioproducts, including biofuels. In addition to expanding the number and diversity of conventional petrochemical replacements that can be synthesized microbially through the creation of enzyme pathways, this project further seeks to explore strategies for engineering more tolerant microbes in support of enhanced chemical production. Novel enzyme pathways will first be engineered to enable the individual biosynthesis of four aromatic products: styrene, (S)-styrene oxide, (R)-styrene glycol, and 2-phenylethanol. To counter the inhibitory effects associated with microbial chemical production, strategies will be explored to improve tolerance and productivity by actively excreting toxic products from cells as they are synthesized. This will be achieved with the aid of both native and heterologous efflux transporter proteins. Finally, novel gene circuits will be engineered to control the expression of efflux pumps only if and when needed by the cell, thereby allowing cells to conserve valuable resources for further chemical production. The development of novel, aromatic-inducible gene circuits to control transporter expression will demonstrate how self-actuating control strategies can be used to maintain maximal host fitness by affording cells the ability to sense and respond to dynamic changes in their environment and intrinsic metabolism. The close integration of the research with educational and outreach activities will be a key component of this project.This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology.