Liu Bo, Tao Yong
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Sheng Wu Gong Cheng Xue Bao. 2019 Oct 25;35(10):1942-1954. doi: 10.13345/j.cjb.190270.
The chemical manufacturing industry that uses fossil resources as raw materials, consumes non-renewable resources and also causes damage to the ecological environment, stimulating the development of bio-manufacturing with renewable resources as raw materials. Unlike traditional chemical manufacturing, bio-manufacturing uses cells as a "production workshop", and each process in the "workshop" is catalyzed by enzymes. In addition to mild reaction conditions, the "cell factory" has strong plasticity, and can be used to synthesize various target chemicals according to demand adjustment or reconstitution of metabolic pathways. The design process of the "cell factory" follows the following guidelines: 1) Construct an optimal synthetic route from raw materials to products; 2) Balance the metabolic flux of each reaction in the metabolic pathway, so that the metabolic flux of this pathway is much higher than the primary metabolism of the cells; 3) Precursor supply in the pathway should be sufficient, and adjust multiple precursors supply ratio as needed; 4) enzymatic reactions often involve the participation of various cofactors, smooth metabolic pathways need to balance or regenerate various cofactors; 5) Through genetic modification or process improvement to remove metabolic intermediates and products feedback inhibition to achieve higher yields.
以化石资源为原料的化学制造业消耗不可再生资源,还会对生态环境造成破坏,这刺激了以可再生资源为原料的生物制造的发展。与传统化学制造不同,生物制造将细胞用作“生产车间”,“车间”内的每个过程都由酶催化。除了反应条件温和外,“细胞工厂”还具有很强的可塑性,可根据需求调整或重构代谢途径来合成各种目标化学品。“细胞工厂”的设计过程遵循以下准则:1)构建从原料到产品的最优合成路线;2)平衡代谢途径中各反应的代谢通量,使该途径的代谢通量远高于细胞的初级代谢;3)途径中的前体供应应充足,并根据需要调整多种前体的供应比例;4)酶促反应常涉及各种辅因子的参与,顺畅的代谢途径需要平衡或再生各种辅因子;5)通过基因改造或工艺改进消除代谢中间体和产物的反馈抑制以实现更高产量。