BRITE Future: Bioeconomy Relevant Innovation Through EASy

加快生物制造和减少对提炼石油以获得商品化学品的依赖是国家的优先事项。这个项目的重点是开发技术和细菌菌株，使工业上重要的化合物能够从可再生资源而不是化石燃料中制造出来。为了实现这一目标，可以利用细菌合成复杂化学物质的能力。在需求量很大的石油化工产品中，芳香族化合物可以由细菌合成。然而，自然生物合成途径需要修改，以使特定化合物的高水平积累在经济上可行。本项目涉及对贝氏不动杆菌和恶臭假单胞菌两种土壤细菌的生物合成途径进行改造，以生产芳香族化合物。这项研究是通过与阿贡国家实验室的一组科学家合作完成的。这种合作既有科学成分，也有教育成分。学生们通过一系列研讨会了解生物制造和代谢工程，以及在这些领域的职业生涯，这些研讨会以敏捷生物制造的科学家为特色。这项研究的长期目标是创造一种具有成本效益的生物合成途径，使细菌将植物来源的糖转化为工业上需要的芳香族化合物。这些化合物需求量很大，现在作为石油化工产品在商业上可以买到。研究中使用的细菌，baylyacinetobacter ADP1和Pseudomonas putida KT2440，利用shikimate途径合成芳香族化合物。为了增加碳通量进入生物合成，一种不属于莽草酸途径的酶被新的诱变和适应性实验室进化方法改变，并在baylyi中进行了研究。这种细菌具有非常高的自然转化和等位基因替换效率，并可作为产生新型酶的宿主。利用baylyi中产生的一种新酶，在p.p putida中设计了一种改良的莽草酸途径。这一策略利用两种不同的细菌以一种互补的方式，利用每种细菌的独特特征。预计恶臭杆菌的工程途径可以将可再生生物质原料中的碳重定向到高水平的所需最终产品中。与来自Agile bioffoundry的研究人员合作，采用高通量技术，使用先进的分析和基于微流体的技术来实现项目目标。该奖项由分子和细胞生物科学部的系统和合成生物学项目以及化学生物工程环境和运输系统部的细胞和生化工程项目共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

It is a national priority to accelerate biomanufacturing and to reduce dependence on refining petroleum to obtain commodity chemicals. This project focuses on developing techniques and bacterial strains that will allow industrially important compounds to be made from renewable resources rather than from fossil fuels. Towards this goal, the ability of bacteria to synthesize complex chemicals can be exploited. Among the petrochemicals in high demand are aromatic compounds that can be made by bacteria. However, natural biosynthetic pathways need to be modified to allow the accumulation of specific compounds at high levels to be economically feasible. This project involves the modification of a biosynthetic pathway in two kinds of soil bacteria, Acinetobacter baylyi and Pseudomonas putida to produce aromatic compounds. The research is accomplished through a collaboration with a team of scientists at Argonne National Laboratory. This collaboration has both scientific and educational components. Students learn about biomanufacturing and metabolic engineering, as well as careers in these fields, through a seminar series featuring scientists of the Agile BioFoundry. The long-term goal of this research is to create a cost-effective biosynthetic route for the bacterial conversion of plant-derived sugars to industrially needed aromatic compounds. Such compounds are in high demand and are commercially available now as petrochemicals. The bacteria employed in the research, Acinetobacter baylyi ADP1 and Pseudomonas putida KT2440, use the shikimate pathway to make aromatic compounds. To increase carbon flux into biosynthesis, an enzyme that is not typically part of the shikimate pathway is altered by novel mutagenesis and adaptive laboratory evolution methods and investigated in A. baylyi. This bacterium has an exceptionally high efficiency of natural transformation and allelic replacement and serves as host to generate novel enzymes. A modified shikimate pathway is engineered in P. putida using one of the novel enzymes generated in A. baylyi. This strategy uses the two different kinds of bacteria in a complementary approach that exploits unique features of each. The engineered pathway in P. putida is predicted to redirect carbon from a renewable biomass feedstock into high levels of desired end products. The collaboration with researchers from the Agile BioFoundry employs high throughput techniques to accomplish the project goals using advanced analytics and microfluidics-based techniques.This award is co-funded by the Systems and Synthetic Biology program in the Division of Molecular and Cellular Biosciences and the Cellular and Biochemical Engineering program in the Division of Chemical Bioengineering Environmental and Transport Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.