Department of Chemical Engineering & Applied Chemistry, University of Toronto, Toronto, ON M5T 3E5, Canada.
Institute of Biomedical Engineering, 164 College St., Toronto, ON M5S 3E2, Canada.
J Ind Microbiol Biotechnol. 2024 Jan 9;51. doi: 10.1093/jimb/kuae027.
Chain elongating bacteria are a unique guild of strictly anaerobic bacteria that have garnered interest for sustainable chemical manufacturing from carbon-rich wet and gaseous waste streams. They produce C6-C8 medium-chain fatty acids, which are valuable platform chemicals that can be used directly, or derivatized to service a wide range of chemical industries. However, the application of chain elongating bacteria for synthesizing products beyond C6-C8 medium-chain fatty acids has not been evaluated. In this study, we assess the feasibility of expanding the product spectrum of chain elongating bacteria to C9-C12 fatty acids, along with the synthesis of C6 fatty alcohols, dicarboxylic acids, diols, and methyl ketones. We propose several metabolic engineering strategies to accomplish these conversions in chain elongating bacteria and utilize constraint-based metabolic modelling to predict pathway stoichiometries, assess thermodynamic feasibility, and estimate ATP and product yields. We also evaluate how producing alternative products impacts the growth rate of chain elongating bacteria via resource allocation modelling, revealing a trade-off between product chain length and class versus cell growth rate. Together, these results highlight the potential for using chain elongating bacteria as a platform for diverse oleochemical biomanufacturing and offer a starting point for guiding future metabolic engineering efforts aimed at expanding their product range.
ONE-SENTENCE SUMMARY: In this work, the authors use constraint-based metabolic modelling and enzyme cost minimization to assess the feasibility of using metabolic engineering to expand the product spectrum of anaerobic chain elongating bacteria.
链伸长菌是一类独特的严格厌氧细菌，它们从富含碳的湿气体废物流中获取可持续化学制造的兴趣。它们产生 C6-C8 中链脂肪酸，这是有价值的平台化学品，可以直接使用，也可以衍生化以服务于广泛的化学工业。然而，链伸长菌在合成 C6-C8 中链脂肪酸以外的产品方面的应用尚未得到评估。在这项研究中，我们评估了扩大链伸长菌产品谱至 C9-C12 脂肪酸以及 C6 脂肪酸醇、二羧酸、二醇和甲基酮合成的可行性。我们提出了几种代谢工程策略来实现链伸长菌中的这些转化，并利用基于约束的代谢建模来预测途径化学计量、评估热力学可行性和估计 ATP 和产物产率。我们还通过资源分配建模评估了生产替代产品如何影响链伸长菌的生长速率，揭示了产物链长与类与细胞生长速率之间的权衡。总之，这些结果强调了使用链伸长菌作为多样化油脂化学制造平台的潜力，并为指导未来旨在扩大其产品范围的代谢工程努力提供了起点。
在这项工作中，作者使用基于约束的代谢建模和酶成本最小化来评估使用代谢工程扩展厌氧链伸长细菌产物谱的可行性。
