Li Yang, Yang Shujie, Ma Danlei, Song Wei, Gao Cong, Liu Liming, Chen Xiulai
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China.
Nat Prod Rep. 2021 Aug 1;38(8):1518-1546. doi: 10.1039/d0np00062k. Epub 2021 Jan 7.
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 C-C 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.
截至2020年底
有机酸作为基础化合物，已在食品、制药、塑料和化工行业中广泛应用。到目前为止，化学合成仍然是工业规模生产有机酸的主要方法。然而，这一过程面临一些不可避免的挑战，如石油资源枯竭、反应条件苛刻以及下游工艺复杂。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景的方法。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对微生物细胞工厂进行重新编程以生产有机酸，包括一元羧酸、羟基羧酸、氨基羧酸、二元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形成、增强代谢通量以促进产物生物合成、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。在此，我们描述了通过代谢工程策略生产碳 - 碳有机酸的最新进展。此外，我们对于何时、采取何种以及如何采取这些策略提供了新的见解。还讨论了在进一步推进微生物工程和建立高效生物精炼厂方面未来面临的挑战。
