SusChEM: Enhancing Tolerance and Performance of a Renewable Aromatic Biorefinery

1511637大卫·尼尔森虽然可以通过工程将可再生生物质转化为一系列有用的化学物质，但同样的产品往往会抑制产生微生物的生产力。该项目旨在探索设计耐受性更强的微生物以支持提高化学生产的策略。将首先设计新的酶途径，使目前从石油中提取的四种芳香族产品能够单独生物合成。它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。在该项目中开发的材料和战略最终不仅将使可再生芳香化学品的生产受益，而且还将使包括生物燃料在内的一系列其他有用的生物产品受益。除了扩大可通过创建酶途径进行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培育耐受性更强的微生物以支持提高化学生产的策略。将首先设计新的酶途径，使四种芳香族产品能够单独生物合成：苯乙烯、(S)-环氧苯乙烷、(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泄有毒产物来提高耐受性和生产率的策略。这将在天然和异源外排转运蛋白的帮助下实现。最后，将设计新的基因电路，仅在细胞需要时才控制外排泵的表达，从而使细胞能够为进一步的化学生产节省宝贵的资源。控制转运蛋白表达的新型芳香族诱导基因电路的开发将展示如何使用自启动控制策略，通过赋予细胞感知和响应环境和内在代谢的动态变化的能力来保持最大的宿主适应性。这项研究与教育和推广活动的紧密结合将是这一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获得，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.