Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, United States; DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Wisconsin-Madison, Madison, WI 53706, United States.
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, United States; DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Wisconsin-Madison, Madison, WI 53706, United States; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI 53706, United States.
Metab Eng. 2020 Mar;58:35-46. doi: 10.1016/j.ymben.2019.04.009. Epub 2019 Apr 22.
Microbial production of oleochemicals from renewable feedstocks remains an attractive route to produce high-energy density, liquid transportation fuels and high-value chemical products. Metabolic engineering strategies have been applied to demonstrate production of a wide range of oleochemicals, including free fatty acids, fatty alcohols, esters, olefins, alkanes, ketones, and polyesters in both bacteria and yeast. The majority of these demonstrations synthesized products containing long-chain fatty acids. These successes motivated additional effort to produce analogous molecules comprised of medium-chain fatty acids, molecules that are less common in natural oils and therefore of higher commercial value. Substantial progress has been made towards producing a subset of these chemicals, but significant work remains for most. The other primary challenge to producing oleochemicals in microbes is improving the performance, in terms of yield, rate, and titer, of biocatalysts such that economic large-scale processes are feasible. Common metabolic engineering strategies include blocking pathways that compete with synthesis of oleochemical building blocks and/or consume products, pulling flux through pathways by removing regulatory signals, pushing flux into biosynthesis by overexpressing rate-limiting enzymes, and engineering cells to tolerate the presence of oleochemical products. In this review, we describe the basic fundamentals of oleochemical synthesis and summarize advances since 2013 towards improving performance of heterotrophic microbial cell factories.
从可再生原料生产油脂化学品仍然是生产高能量密度、液体运输燃料和高价值化学品的有吸引力的途径。代谢工程策略已被应用于证明生产各种油脂化学品，包括细菌和酵母中的游离脂肪酸、脂肪醇、酯、烯烃、烷烃、酮和聚酯。这些演示中的大多数都合成了含有长链脂肪酸的产品。这些成功促使人们进一步努力生产类似的由中链脂肪酸组成的分子，这些分子在天然油脂中较少见，因此具有更高的商业价值。在生产这些化学物质的子集方面已经取得了重大进展，但对于大多数化学物质来说，仍有大量工作要做。在微生物中生产油脂化学品的另一个主要挑战是提高生物催化剂的性能，就产率、速率和浓度而言，以便经济可行的大规模工艺。常见的代谢工程策略包括阻断与油脂化学构建块合成竞争的途径和/或消耗产物的途径，通过去除调节信号来拉动途径中的通量，通过过表达限速酶来推动通量进入生物合成，以及工程细胞以耐受油脂化学品产物的存在。在这篇综述中，我们描述了油脂化学合成的基本原理，并总结了自 2013 年以来在提高异养微生物细胞工厂性能方面的进展。
