SusChEM: Enhancing Tolerance and Performance of a Renewable Aromatic Biorefinery

大卫1511637 尽管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品，但相同的产品通常会抑制生产微生物的生产力。 该项目旨在探索工程更耐受微生物的策略，以支持增强化学品生产。 首先将设计新的酶途径，使目前从石油中衍生的四种芳香族产品能够单独生物合成。他们的替代生物生产最终将有助于减少美国对外国石油和天然气的依赖。该项目中开发的材料和策略最终将不仅有利于可再生芳香族化学品的生产，而且有利于包括生物燃料在内的其他各种有用的生物产品。除了扩大可以通过创建酶途径微生物合成的传统石化替代品的数量和多样性外，该项目还寻求探索工程化更耐受微生物的策略，以支持增强化学品生产。 新的酶途径将首先被设计成能够单独生物合成四种芳香族产物：苯乙烯、（S）-氧化苯乙烯、（R）-苯乙烯乙二醇和2-苯基乙醇。 为了对抗与微生物化学生产相关的抑制作用，将探索通过在合成时从细胞中主动排泄有毒产物来提高耐受性和生产力的策略。 这将在天然和异源外排转运蛋白的帮助下实现。最后，新的基因电路将被设计成仅在细胞需要时控制外排泵的表达，从而使细胞能够保存宝贵的资源用于进一步的化学生产。开发新的芳香诱导基因电路来控制转运蛋白的表达，将展示如何使用自启动控制策略，通过使细胞能够感知和响应环境和内在代谢的动态变化，来维持最大的宿主适应性。该研究与教育和推广活动的紧密结合将是该项目的关键组成部分。该奖项由CBET部门的生物技术和生物化学工程计划共同资助，由分子和细胞生物学部门的系统和合成生物学计划共同资助。

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.