A kinetic framework for modeling oleochemical biosynthesis in Escherichia coli,Biotechnology and Bioengineering

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A kinetic framework for modeling oleochemical biosynthesis in Escherichia coli
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2022-08-12 , DOI: 10.1002/bit.28209
Jackson Peoples ₁ , Sophia Ruppe ₁ , Kathryn Mains ₁ , Elia C Cipriano ₁ , Jerome M Fox ₁

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Microorganisms build fatty acids with biocatalytic assembly lines, or fatty acid synthases (FASs), that can be repurposed to produce a broad set of fuels and chemicals. Despite their versatility, the product profiles of FAS-based pathways are challenging to adjust without experimental iteration, and off-target products are common. This study uses a detailed kinetic model of the Escherichia coli FAS as a foundation to model nine oleochemical pathways. These models provide good fits to experimental data and help explain unexpected results from in vivo studies. An analysis of pathways for alkanes and fatty acid ethyl esters (FAEEs), for example, suggests that reductions in titer caused by enzyme overexpression—an experimentally consistent phenomenon—can result from shifts in metabolite pools that are incompatible with the substrate specificities of downstream enzymes, and a focused examination of multiple alcohol pathways indicates that coordinated shifts in enzyme concentrations provide a general means of tuning the product profiles of pathways with promiscuous components. The study concludes by integrating all models into a graphical user interface. The models supplied by this work provide a versatile kinetic framework for studying oleochemical pathways in different biochemical contexts.

中文翻译：

模拟大肠杆菌油脂化学生物合成的动力学框架

微生物通过生物催化装配线或脂肪酸合酶 (FAS) 构建脂肪酸，可将其重新用于生产多种燃料和化学品。尽管具有多功能性，但基于 FAS 的途径的产品配置文件在没有实验迭代的情况下难以调整，并且脱靶产品很常见。本研究使用大肠杆菌的详细动力学模型FAS 作为模拟九种油脂化学途径的基础。这些模型很好地拟合了实验数据，并有助于解释体内研究的意外结果。例如，对烷烃和脂肪酸乙酯 (FAEE) 途径的分析表明，由酶过度表达引起的滴度降低（一种实验上一致的现象）可能是由于代谢物库的变化与下游酶的底物特异性不相容造成的，并且对多种酒精途径的集中检查表明，酶浓度的协调变化提供了一种调整具有混杂成分的途径的产物谱的通用方法。该研究通过将所有模型集成到图形用户界面中来结束。

更新日期：2022-08-12

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