Overexpression of key enzymes of the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for improving squalene production in Escherichia coli

Haiyuan Liu; Shu Han; Liping Xie; Jie Pan; Wei Zhang; Guihua Gong; Youjia Hu

doi:10.5897/AJB2017.16235

African Journal of
Biotechnology

Abbreviation: Afr. J. Biotechnol.
Language: English
ISSN: 1684-5315
DOI: 10.5897/AJB
Start Year: 2002
Published Articles: 12487

Full Length Research Paper

Overexpression of key enzymes of the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for improving squalene production in Escherichia coli

Haiyuan Liu

Haiyuan Liu
China State Institute of Pharmaceutical Industry, Zhangjiang Insitute, Shanghai 201203, China.
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Shu Han

Shu Han
China State Institute of Pharmaceutical Industry, Zhangjiang Insitute, Shanghai 201203, China.
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Liping Xie

Liping Xie
China State Institute of Pharmaceutical Industry, Zhangjiang Insitute, Shanghai 201203, China.
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Jie Pan

Jie Pan
China State Institute of Pharmaceutical Industry, Zhangjiang Insitute, Shanghai 201203, China.
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Wei Zhang

Wei Zhang
China State Institute of Pharmaceutical Industry, Zhangjiang Insitute, Shanghai 201203, China.
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Guihua Gong

Guihua Gong
China State Institute of Pharmaceutical Industry, Zhangjiang Insitute, Shanghai 201203, China.
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Youjia Hu

Youjia Hu
China State Institute of Pharmaceutical Industry, Zhangjiang Insitute, Shanghai 201203, China.
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Article Number - CBA29D767138
Vol.16(50), pp. 2307-2316 , December 2017
https://doi.org/10.5897/AJB2017.16235

Received: 07 September 2017
Accepted: 16 November 2017
Published: 13 December 2017

Abstract

2-C-Methyl-D-erythritol-4-phosphate (MEP) pathway has been extensively employed for terpenoids biosynthesis in Escherichia coli. In this study, to obtain key-enzymes of MEP pathway for squalene production, overexpression of different combination of MEP pathway genes were compared. Squalene production in strain YSS12 with overexpressed dxs, idi and ispA of MEP pathway from E. coli was improved by 71-fold when compared with strain YSS3 which only contained double copy SQS. Analysis of transcriptional levels of MEP pathway genes in engineering strains showed that different squalene production can be attributed to changed transcriptional levels of co-overexpressed genes dxs, idi, ispG and ispA in engineering strains. Furthermore, different E. coli expression hosts were compared for squalene production, among which BL21(DE3) was the best squalene producer. These results illustrate that dxs, idi and ispA of the MEP pathway from E. coli were key-enzymes for squalene production in E. coli. These key-enzymes of MEP pathway could also be applied to other terpenoids production in E. coli.