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作 者:孙青 刘德华[1,2] 陈振 SUN Qing;LIU De-hua;CHEN Zhen(Key Laboratory of Industrial Biocatalysis(Ministry of Education),Department of Chemical Engineering,Tsinghua University,Beijing 100084,China;Center for Synthetic and Systems Biology,Tsinghua University,Beijing 100084,China)
机构地区:[1]清华大学化学工程系,工业生物催化教育部重点实验室,北京100084 [2]清华大学合成与系统生物学中心,北京100084
出 处:《中国生物工程杂志》2020年第10期65-75,共11页China Biotechnology
基 金:国家重点研发计划(2018YFA0901500)资助项目。
摘 要:甲醇作为一种来源广泛、价格低廉、还原度高的非粮原料有望成为下一代生物制造的关键原料。利用合成生物学技术构建能够高效利用甲醇的重组微生物以实现从甲醇到高值化学品的生物转化已成国内外研究热点,但由于甲醇代谢过程的特殊性及复杂性,目前人工设计的甲基营养菌还难以实现以甲醇为唯一碳源进行生长及产物合成。基于对天然甲基营养菌甲醇代谢过程的分析,从甲醇脱氢酶的筛选与改造、甲醛同化途径的重构与优化、甲醇到化学品的生物转化几个方面对合成型甲基营养菌的构建策略及面临的挑战进行总结与分析,以期为今后合成型甲基营养菌的人工设计和利用提供一定的借鉴。Methanol is an abundant raw material with low price and high reduction degree,which is expected to be a promising feedstock for the next generation biomanufacturing.To convert methanol into valueadded chemicals,constructing recombinant microorganisms using synthetic biology has received broad attention in recent years.However,due to the complex regulation of methanol metabolism,the current engineered synthetic methylotrophy still cannot use methanol as the sole carbon source for growth and chemical production.Based on the analysis of methanol metabolic mechanism in natural methylotrophy,this review summarized the main challenges for designing and constructing synthetic methylotrophy and proposed potential strategies to overcome these barriers.Especially,it focused on the following aspects,including:screening and engineering methanol dehydrogenase;optimizing and balancing formaldehyde assimilation pathways;bioconversion of methanol to chemicals.
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