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微生物所创建非天然化学品1,2,4-丁三醇生物合成新途径

摘要 : 中国科学院微生物生理与代谢工程重点实验室的研究人员,根据基团反应原理和吉布斯自由能计算,设计了一条热力学上可行的1,2,4-丁三醇生物合成新途径。相关文章发表于2014年7月10日的《Scientific Reports》杂志上,研究成果已获得中国专利授权。

合成生物学旨在设计和创建新的生物学元件、组件/装置和系统,或者通过对天然生物系统的重新设计,获得具有特定功能的人工生命体系,来解决人类面临的资源、能源、环境和健康问题。近年来,随着合成生物学的快速发展,创建非天然化学品的生物合成途径,成为一个新的研究热点。

1,2,4-丁三醇是一种重要的有机合成中间体,在医药、烟草、化妆品、造纸、农业和高分子材料领域具有广泛用途。其硝基化合物1,2,4-丁三醇三硝酸酯是一种高能增塑剂,可替代硝化甘油用于火箭、导弹、炸药等军工领域。自然界中尚未发现天然的1,2,4-丁三醇生物合成途径,故1,2,4-丁三醇只能通过化学合成方法获得,得率低,价格高昂。

中国科学院微生物生理与代谢工程重点实验室的研究人员,根据基团反应原理和吉布斯自由能计算,设计了一条热力学上可行的1,2,4-丁三醇生物合成新途径。该途径始于L-苹果酸,经六步反应生成L-1,2,4-丁三醇。将该途径与葡萄糖到苹果酸的途径连接后,1,2,4-丁三醇的最大理论得率可达0.65 g/g葡萄糖,与化学合成路线相比具有较强的竞争力。在完成理论设计的基础上,研究人员通过关键酶基因的挖掘、合成和表达调控,成功创建了从苹果酸到1,2,4-丁三醇的生物合成途径,实现以葡萄糖为唯一碳源生物合成1,2,4-丁三醇,为降低1,2,4-丁三醇的生产成本提供了可能。

该研究由博士后李兴华在张延平副研究员和蔡真助理研究员指导下完成。研究成果已获得中国专利授权,并于7月10日发表在自然出版集团的Scientific Reports上。研究得到中国科学院知识创新工程重要方向项目和北京市自然科学基金的资助。

原文摘要:

Design and Construction of a Non-Natural Malate to 1,2,4-Butanetriol Pathway Creates Possibility to Produce 1,2,4-Butanetriol from Glucose

Xinghua Li, Zhen Cai, Yin Li & Yanping Zhang

1,2,4-butanetriol (BT) is an important bulk chemical mainly used for producing the superior energetic plasticizer (1,2,4-butanetriol trinitrate) in propellant and explosive formulations. BT is commercially produced by chemical synthesis from petroleum-based feedstocks; until recently a costly biosynthetic route from xylose or arabinose was reported. Here we designed a novel biosynthetic pathway for BT from malate, for the purpose of using glucose as an alternative and cheaper substrate in future. This biosynthetic pathway was achieved through six sequential enzymatic reactions. Following tests of several combinations of enzymes for the pathway, five enzymes including malate thiokinase, succinate-semialdehyde dehydrogenase, 4-hydroxybutyrate dehydrogenase, 4-hydroxybutyrate CoA-transferase and bifunctional aldehyde/alcohol dehydrogenase were finally chosen. All enzyme genes were expressed on two compatible plasmids in E. coli, and their functions verified separately. Following assembly of two functional modules, BT was detected in the fermentation broth upon addition of malate, proving BT can be biosynthesized from malate. Furthermore, BT was detected in the fermentation using glucose as the sole carbon source, suggesting that such novel BT biosynthetic pathway has created the possibility for the production of BT from the cheaper substrate glucose.

 

来源: 中科院 浏览次数:46

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