Elucidating and Computing Metabolic Networks for Co-Valorization of Cellulose and Lignin Derivatives

将树木和植物中的木质素和纤维素转化为有价值的产品可以减少我们对石油和天然气等不可再生原料的依赖。假单胞菌属是一种具有强大和多样代谢的土壤细菌。因此，它们可以产生各种潜在的重要分子。该项目将开发假单胞菌加工木质素和纤维素的详细途径图。这些途径的调节也将被研究。该项目将为本科生提供研究机会，并将在当地一所高中让妇女参与STEM外联活动。该项目旨在了解野生型和工程化恶臭假单胞菌菌株的代谢网络机制。来自纤维素和半纤维素的糖和来自木质素的芳族底物的混合底物利用将是主要焦点。有三个具体目标。首先，阐明了同时处理来自纤维素和木质素单体的碳的代谢结构。第二，定量分析代谢网络向相关生物合成途径的通量。第三，识别网络中受调节控制的代谢节点。该项目将采用稳定同位素辅助代谢组学，蛋白质组学分析，基因组规模的定量通量建模和最佳代谢编程的计算机预测相结合。这项研究的长期目标是解开代谢途径的限制，将木质纤维素原料衍生物转化为增值的构建模块。（ENG/CBET）和系统与合成生物学（BIO/MCB）该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准。

Conversion of lignin and cellulose from trees and plants into valuable products could reduce our reliance on non-renewable feedstocks such as petroleum and natural gas. Pseudomonas are species of soil bacteria with robust and varied metabolisms. As a result, they can produce a variety of potentially important molecules. This project will develop a detailed map of the pathways involved in processing lignin and cellulose by Pseudomonas. The regulation of these pathways will also be studied. The project will extend research opportunities to undergraduates and will engage women with STEM outreach activities at a local high school. The project aims to understand the mechanisms of the metabolic networks in wild-type and engineered Pseudomonas putida strains. Mixed-substrate utilization of sugars from cellulose and hemicellulose, and aromatic substrates from lignin will be the primary focus. There are three specific objectives. First, elucidate the metabolic architecture for simultaneous processing of carbons derived from cellulose and lignin monomers. Second, analyze the metabolic network fluxes towards relevant biosynthetic pathways quantitatively. Third, identify the metabolic nodes under regulatory control in the network. The project will employ a combination of stable isotope-assisted metabolomics, proteomics profiling, genome-scale quantitative flux modeling, and in silico predictions of optimal metabolic programming. The long-term goal of this research is to unravel metabolic pathway limitations to converting lignocellulosic feedstock derivatives to value-added building blocks.This project is being supported jointly by the Cellular and Biochemical Engineering (ENG/CBET) and the Systems and Synthetic Biology (BIO/MCB) Programs.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.