文献类型：期刊文献

英文题名：In silico Analysis and Experimental Improvement of Taxadiene Heterologous Biosynthesis in Escherichia coli

作者：Meng, Hailin[1,2,3];Wang, Yong[2];Hua, Qiang[3];Zhang, Siliang[3];Wang, Xiaoning[1]

机构：[1]S China Univ Technol, Sch Biosci & Bioengn, Guangzhou 510641, Guangdong, Peoples R China;[2]Chinese Acad Sci, Key Lab Synthet Biol, Inst Biol Sci, Shanghai 200032, Peoples R China;[3]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Natl Engn Res Ctr Biotechnol, Shanghai 200237, Peoples R China

年份：2011

卷号：16

期号：2

起止页码：205

外文期刊名：BIOTECHNOLOGY AND BIOPROCESS ENGINEERING

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000290070800001)】；

基金：This study was sponsored by "Shanghai Pujiang Program 09PJ1403600", and supported by the "National Special Fund for State Key Laboratory of Bioreactor Engineering (Grant No. 2060204)", the "Key New Drug Creation and Development Program: 2008ZX09401-05", the "National Natural Science Foundation of China (General Program, Grant No. 31070030)", and the "Major Projects of Knowledge Innovation Program of Chinese Academy of Sciences (Grant No. KSCX2-EW-J-12)".

语种：英文

外文关键词：taxadiene; isopentenyl pyrophosphate; heterologous biosynthesis; in silico analysis; pathway engineering

摘要：The biosynthesis of terpenoids in heterologous hosts has become increasingly popular. Isopentenyl diphosphate (IPP) is the central precursor of all isoprenoids, and the synthesis can proceed via two separate pathways in different organisms: The 1-deoxylulose 5-phosphate (DXP) pathway and the mevalonate (MVA) pathway. In this study, an in silico comparison was made between the maximum theoretical IPP yields and the thermodynamic properties of the DXP and MVA pathways using different hosts and carbon sources. We found that Escherichia coli and its DXP pathway have the most potential for IPP production. Consequently, codon usage redesign, and combinations of chromosomal engineering and various strains were considered for optimizing taxadiene biosynthesis through the endogenic DXP pathway. A high production strain yielding 876 +/- 60 mg/L taxadiene, with an overall volumetric productivity of 8.9 mg/(L x h), was successfully obtained by combining the chromosomal engineered upstream DXP pathway and the downstream taxadiene biosynthesis pathway. This is the highest yield thus far reported for taxadiene production in a heterologous host. These results indicate that genetic manipulation of the DXP pathway has great potential to be used for production of terpenoids, and that chromosomal engineering is a powerful tool for heterologous biosynthesis of natural products.