Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, USA.
Centre for Sustainable Future Technologies, Fondazione Istituto Italiano di Tecnologia, Turin, Italy.
mSystems. 2022 Apr 26;7(2):e0111121. doi: 10.1128/msystems.01111-21. Epub 2022 Mar 24.
Gas fermentation provides a promising platform to turn low-cost and readily available single-carbon waste gases into commodity chemicals, such as 2,3-butanediol. Clostridium autoethanogenum is usually used as a robust and flexible chassis for gas fermentation. Here, we leveraged constraint-based stoichiometric modeling and kinetic ensemble modeling of the metabolic network to provide a systematic analysis of metabolic engineering interventions for 2,3-butanediol overproduction and low carbon substrate loss in dissipated CO. Our analysis allowed us to identify and to assess comparatively the expected performances for a wide range of single, double, and triple interventions. Our analysis managed to individuate bottleneck reactions in relevant metabolic pathways when suggesting intervening strategies. Besides recapitulating intuitive and/or previously attempted genetic modifications, our analysis neatly outlined that interventions-at least partially-impinging on by-products branching from acetyl coenzyme A (acetyl-CoA) and pyruvate (acetate, ethanol, amino acids) offer valuable alternatives to the interventions focusing directly on the specific branch from pyruvate to 2,3-butanediol. Envisioning value chains inspired by environmental sustainability and circularity in economic models is essential to counteract the alterations in the global natural carbon cycle induced by humans. Recycling carbon-based waste gas streams into chemicals by devising gas fermentation bioprocesses mediated by acetogens of the genus is one component of the solution. Carbon monoxide originates from multiple biogenic and abiogenic sources and bears a significant environmental impact. This study aims at identifying metabolic engineering interventions for increasing 2,3-butanediol production and avoiding carbon loss in CO dissipation via fermenting a substrate comprising CO and H. 2,3-Butanediol is a valuable biochemical by-product since, due to its versatility, can be transformed quite easily into chemical compounds such as butadiene, diacetyl, acetoin, and methyl ethyl ketone. These compounds are usable as building blocks to manufacture a vast range of industrially produced chemicals.
气体发酵为将低成本且易得的单碳废气转化为商品化学品（如 2,3-丁二醇）提供了一个很有前途的平台。产酸克雷伯氏菌通常被用作气体发酵的强大且灵活的底盘。在这里，我们利用基于约束的代谢网络平衡态和动态集合模型，对 2,3-丁二醇的过量生产和 CO 耗散中低碳底物损失的代谢工程干预进行了系统分析。我们的分析使我们能够识别和评估广泛的单、双和三重干预措施的预期性能。当提出干预策略时，我们的分析能够确定并评估相关代谢途径中的瓶颈反应。除了概括直观的和/或以前尝试过的遗传修饰外，我们的分析还清楚地表明，干预措施-至少部分地影响来自乙酰辅酶 A（乙酰辅酶 A）和丙酮酸（乙酸盐、乙醇、氨基酸）的副产物分支-为直接针对从丙酮酸到 2,3-丁二醇的特定分支的干预措施提供了有价值的替代方案。在经济模型中，设想基于环境可持续性和循环性的价值链对于抵消人类引起的全球自然碳循环的变化至关重要。通过设计由产乙酸菌介导的气体发酵生物过程，将基于碳的废气流回收为化学品是解决方案的一部分。一氧化碳来源于多种生物和非生物来源，对环境有重大影响。本研究旨在通过发酵包含 CO 和 H 2 的底物，确定用于提高 2,3-丁二醇产量和避免 CO 耗散中碳损失的代谢工程干预措施。2,3-丁二醇是一种有价值的生化副产物，因为由于其多功能性，它可以很容易地转化为丁二烯、双乙酰、乙酰基丙铜和甲基乙基酮等化合物。这些化合物可用作制造各种工业化学品的基础材料。
