Abstract
3-Hydroxypropionate (3HP) is an important platform chemical, and four 3HP biosynthetic routes were reported, in which the malonyl-CoA pathway has some expected advantages but presented the lowest 3HP yield. Here, we demonstrated that this low yield was caused by a serious functional imbalance between MCR-C and MCR-N proteins, responsible for the two-step reduction of malonyl-CoA to 3HP. Then we minimized the enzyme activity imbalance by directed evolution of rate-limiting enzyme MCR-C and fine tuning of MCR-N expression level. Combined with culture conditions optimization, our engineering approaches increased the 3HP titer 270-fold, from 0.15 g/L to 40.6 g/L, representing the highest 3HP production via malonyl-CoA pathway so far. This study not only significantly improved the 3HP productivity of recombinant Escherichia coli strain, but also proved the importance of metabolic balance in a multistep biosynthetic pathway, which should be always considered in any metabolic engineering study.
References
Jan 11, 1992·Nucleic Acids Research·C J Lohff, K B Cease
Mar 25, 1998·Gene·R A EdwardsD M Schifferli
Oct 10, 2001·Angewandte Chemie·Sean V. TaylorDonald Hilvert
Apr 12, 2002·Journal of Bacteriology·Michael HüglerGeorg Fuchs
Jun 25, 2008·Annual Review of Biophysics·Christian JäckelDonald Hilvert
Jan 22, 2010·Biotechnology and Bioengineering·Christopher S HenryVassily Hatzimanikatis
Feb 27, 2010·Metabolic Engineering·Tiangang LiuChaitan Khosla
Jun 7, 2011·Applied Microbiology and Biotechnology·Yujin CaoMo Xian
Jul 5, 2011·Journal of Biotechnology·Chelladurai RathnasinghSunghoon Park
Nov 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xingye YuChaitan Khosla
Sep 28, 2013·PloS One·Changshui LiuGuang Zhao
Nov 7, 2013·ACS Chemical Biology·Peng XuMattheos A G Koffas
Feb 8, 2014·Metabolic Engineering·Yun ChenJens Nielsen
May 20, 2014·PloS One·Yongqiang GaoGuang Zhao
Jul 23, 2014·Biotechnology Letters·Qi WangGuang Zhao
Jul 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Peng XuMattheos Koffas
Dec 24, 2014·Metabolic Engineering·Qian LiuTiangang Liu
Apr 12, 2015·Metabolic Engineering·Yaping YangYajun Yan
Aug 19, 2015·Metabolic Engineering·Ethan I LanJames C Liao
Citations
Jan 13, 2017·Critical Reviews in Biotechnology·Changshui LiuGuang Zhao
Jan 8, 2017·BMC Microbiology·Min LiuGuang Zhao
Mar 15, 2018·Biotechnology and Bioengineering·Katia TarasavaRyan T Gill
Nov 1, 2017·Microbial Cell Factories·Yi-Ming YangSong Yang
Jun 27, 2018·FEMS Microbiology Reviews·Christopher T StraubRobert M Kelly
Aug 10, 2017·BMC Biotechnology·Rubing ZhangHuizhou Liu
Dec 10, 2019·Environmental Microbiology·Hyeoncheol Francis SonKyung-Jin Kim
Oct 10, 2018·Frontiers in Microbiology·Rong-Yu JiXiao-Jun Ji
Nov 15, 2018·Microbial Cell Factories·Seiya TakayamaAkihiko Kondo
Apr 1, 2020·Biotechnology and Bioengineering·Je Woong KimSang Yup Lee
Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Shenmei SunGuang Zhao
Sep 9, 2017·Applied Microbiology and Biotechnology·Huibin ZouMo Xian
Mar 22, 2020·Nature Communications·Ying XuGuang Zhao
Dec 15, 2020·Acta Biochimica Et Biophysica Sinica·Mingyue FeiDongchang Sun
Dec 6, 2020·Journal of Biotechnology·Shiyun LiYu Deng
Feb 6, 2021·Nature Chemical Biology·Jina YangSang Woo Seo
Feb 25, 2021·ACS Synthetic Biology·Zihua LiZhen Chen
Mar 9, 2021·PLoS Computational Biology·Alexandre OliveiraOscar Dias
Feb 27, 2021·Trends in Biotechnology·Yuwan Liu, Huifeng Jiang
Mar 10, 2021·Nature Communications·Xiao-Ran JiangGuo-Qiang Chen
Dec 12, 2018·Metabolic Engineering·Kento TokuyamaHiroshi Shimizu
Mar 23, 2021·Frontiers in Bioengineering and Biotechnology·Albert Gyapong AduheneChangli Liu
Oct 11, 2016·Journal of Industrial Microbiology & Biotechnology·Zhijie Liu, Tiangang Liu
Jun 4, 2021·Microbial Biotechnology·Albert FinaPau Ferrer
Jun 16, 2021·World Journal of Microbiology & Biotechnology·Peng Zhao, Pingfang Tian
Jun 22, 2021·Frontiers in Bioengineering and Biotechnology·Thanawat BoontipSuchada Chanprateep Napathorn
Jul 20, 2021·Synthetic and Systems Biotechnology·Ningyu LaiHui Wu
Aug 2, 2021·Metabolic Engineering·Ji Yeon LeeGyoo Yeol Jung
Aug 30, 2020·Metabolic Engineering·Xiutao LiuGuang Zhao