Microbial engineering for the production of C2-C6 organic acids.
Microbial engineering for the production of C2-C6 organic acids.
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DOI：
10.1039/d0np00062k
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发表时间：
2021-01
影响因子：
11.9
通讯作者：
Yang Li;Shujie Yang;Danlei Ma;Wei Song;Cong Gao;Liming Liu;Xiulai Chen
中科院分区：
文献类型：
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作者：
Yang Li;Shujie Yang;Danlei Ma;Wei Song;Cong Gao;Liming Liu;Xiulai Chen
覆盖：截至2020年底，有机酸作为结构单元化合物，已广泛应用于食品、制药、塑料和化学工业。迄今为止，化学合成仍然是工业规模生产有机酸的主要方法。然而，这一过程遇到了一些不可避免的挑战，如石油资源的枯竭，苛刻的反应条件和复杂的下游工艺。为了解决这些问题，微生物细胞工厂为实现有机酸的可持续生产提供了一种有前途的方法。然而，中心碳代谢中的一些关键代谢物受到细胞代谢网络的严格调控，导致有机酸的生产率较低。因此，已经开发了多种代谢工程策略来重编程微生物细胞工厂以产生有机酸，包括单羧酸、羟基羧酸、氨基羧酸、二羧酸和聚合物的单体单元。这些策略主要集中在提高酶的催化效率以提高转化率、平衡多基因生物合成途径以减少副产物的形成、加强代谢通量以促进产物的生物合成、优化代谢网络以适应环境条件以及提高底物利用率以拓宽底物谱。本文综述了利用代谢工程技术生产C2-C6有机酸的最新进展。此外，我们提供了新的见解，何时，什么和如何采取这些战略。未来的挑战也讨论了进一步推进微生物工程和建立高效的生物炼油厂。
Covering: up to the end of 2020Organic acids, as building block compounds, have been widely used in food, pharmaceutical, plastic, and chemical industries. Until now, chemical synthesis is still the primary method for industrial-scale organic acid production. However, this process encounters some inevitable challenges, such as depletable petroleum resources, harsh reaction conditions and complex downstream processes. To solve these problems, microbial cell factories provide a promising approach for achieving the sustainable production of organic acids. However, some key metabolites in central carbon metabolism are strictly regulated by the network of cellular metabolism, resulting in the low productivity of organic acids. Thus, multiple metabolic engineering strategies have been developed to reprogram microbial cell factories to produce organic acids, including monocarboxylic acids, hydroxy carboxylic acids, amino carboxylic acids, dicarboxylic acids and monomeric units for polymers. These strategies mainly center on improving the catalytic efficiency of the enzymes to increase the conversion rate, balancing the multi-gene biosynthetic pathways to reduce the byproduct formation, strengthening the metabolic flux to promote the product biosynthesis, optimizing the metabolic network to adapt the environmental conditions and enhancing substrate utilization to broaden the substrate spectrum. Here, we describe the recent advances in producing C2-C6 organic acids by metabolic engineering strategies. In addition, we provide new insights as to when, what and how these strategies should be taken. Future challenges are also discussed in further advancing microbial engineering and establishing efficient biorefineries.