Collaborative Research: Bilateral BBSRC-NSF/BIO: Synthetic Biology for Lignin Utilization

生物学的主要挑战之一是发现将可再生植物基材料转化为商品化学品和燃料的方法。为了使这一过程在经济上可行，有价值的产品必须由木质素制成，木质素是目前大部分未被利用的植物材料的一部分。木质素丰富，其化学成分在生物能源生产和生物技术方面具有巨大的潜力。该项目旨在利用计算和实验生物学中新开发的工具来操纵细菌途径，以改善木质素的降解，最终目标是以可再生方式开发有效的发电方法。一种土壤细菌，baylyacinetobacter ADP1，已经降解了大量植物衍生化合物，将用于这些研究。这种细菌的降解能力将通过向染色体中引入新的基因和优化分解代谢基因的表达来扩大。这个综合项目将通过多学科合作来完成，包括国际合作。培训机会将使学生能够参观和在不同合作者的实验室进行一些研究。所有合作者都致力于培养本科生、研究生和博士后水平的学生。该项目将用于加强科学界的多样性和包容性。本项目将以合成生物学的概念框架为基础，开发baylyi作为受体细胞（底盘），结合遗传模块（装置），扩展芳香化合物分解代谢的细菌途径。为了克服理想概念和生物现实之间的差异可能产生的障碍，一种依赖于基因扩增的新型实验进化方法将有助于优化代谢功能。该方法利用了天麻自然转化和同源重组的超高效率。这种细菌是木质素生物降解的理想基础，因为它具有强大的遗传系统和降解许多芳香化合物的能力，包括那些对大肠杆菌有毒的化合物。实验通量分析和动力学研究将为芳香族化合物分解代谢能力的设计、优化和合成扩展建立动力学模型。该研究小组的一名成员与其他人合作开发的先进计算工具：生化网络集成计算浏览器（BNICE）也将被应用。为了补充这些方法，生物化学、生物物理和结构研究将研究如何利用酶的空间取向来提高催化效率、目标代谢物流动和防止有毒中间体的积累。这个英美合作项目由美国国家科学基金会和英国生物技术和生物科学研究委员会支持。

One of the major challenges in biology is to discover ways to convert renewable plant-based material into commodity chemicals and fuels. For this process to be economically feasible, valuable products must be made from lignin, a portion of plant material that now remains mostly unused. Lignin is abundant and its chemical composition holds great potential for bioenergy production and biotechnology. This project seeks to use newly developed tools in computational and experimental biology to manipulate bacterial pathways for improved lignin degradation with the ultimate goal of developing effective methods of generating energy in a renewable fashion. A soil bacterium, Acinetobacter baylyi ADP1, that already degrades a vast array of plant derived compounds will be used in these studies. The degradation capability of this bacterium will be expanded by introducing new genes into the chromosome and by optimizing the expression of the catabolic genes for the desired applications. This integrative project will be accomplished via a multi-disciplinary collaboration, including an international component. Training opportunities will enable students to visit and conduct some of the research in the laboratories of different collaborators. All collaborators have a strong commitment to training students at the undergraduate, graduate and postdoctoral levels. This project will be used to enhance diversity and inclusiveness in the scientific community.Building on the conceptual framework of synthetic biology, this project will develop A. baylyi as the recipient cell (the chassis) to incorporate genetic modules (devices) to expand bacterial pathways for aromatic compound catabolism. To overcome obstacles that may arise from differences between idealized concepts and biological realities, a novel method of experimental evolution that relies on gene amplification will help optimize metabolic functions. This method exploits the exceptionally high efficiency of natural transformation and homologous recombination in A. baylyi. This bacterium is an ideal chassis for lignin biodegradation because of its powerful genetic system and ability to degrade many aromatic compounds, including those that are toxic to Escherichia coli. Experimental flux analysis and kinetic studies will be used to build dynamical models for the design, optimization, and synthetic expansion of aromatic compound catabolic abilities. Advanced computational tools, developed by a member of this research team, in collaboration with others, will also be applied: Biochemical Network Integrated Computational Explorer (BNICE). To complement these approaches, biochemical, biophysical, and structural studies will examine how the spatial orientation of enzymes can be used to improve catalytic efficiency, target metabolite flow, and prevent toxic intermediates from accumulating.This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.