生物制造“细胞工厂”的设计与组装

Design and assembly of bio-manufacturing “cell factory”

以化石资源为原料的化学品制造行业在消耗不可再生资源的同时,还对生态环境造成了破坏,这给以可再生资源为原料的生物制造带来了发展机遇。与传统化工制造不同,生物制造把细胞作为“生产车间”,“车间”内每一道工序由酶催化完成。“细胞工厂”除了反应条件温和,还具有较强的可塑性,可根据需求调整或者重构代谢途径来合成各种目标化学品。“细胞工厂”的设计过程遵循如下的准则:1)构建一条由原料到产品的最优合成途径;2)平衡代谢途径中每步反应的代谢流,使该途径代谢通量远高于细胞基础代谢;3)足量地供应合成途径的前体,多个前体根据需要调整供应比例;4)酶促反应往往有各种辅因子的参与,顺畅的代谢通路需要平衡或者再生各种辅因子;5)通过遗传改造或者工艺改进解除产物和代谢中间体的反馈抑制,以获取更高的产量。

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.