Biotechnology and Bioprocess Engineering

, Volume 16, Issue 2, pp 205–215

In silico analysis and experimental improvement of taxadiene heterologous biosynthesis in Escherichia coli

  • Hailin Meng
  • Yong Wang
  • Qiang Hua
  • Siliang Zhang
  • Xiaoning Wang
Research Paper

DOI: 10.1007/s12257-010-0329-z

Cite this article as:
Meng, H., Wang, Y., Hua, Q. et al. Biotechnol Bioproc E (2011) 16: 205. doi:10.1007/s12257-010-0329-z

Abstract

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 × 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.

Keywords

taxadieneisopentenyl pyrophosphateheterologous biosynthesisin silico analysispathway engineering

Copyright information

© The Korean Society for Biotechnology and Bioengineering and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Hailin Meng
    • 1
    • 2
    • 3
  • Yong Wang
    • 2
  • Qiang Hua
    • 3
  • Siliang Zhang
    • 3
  • Xiaoning Wang
    • 1
  1. 1.School of Bioscience and BioengineeringSouth China University of TechnologyGuangzhouChina
  2. 2.Key Laboratory of Synthetic Biology, Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  3. 3.State Key Laboratory of Bioreactor Engineering, National Engineering Research Center for BiotechnologyEast China University of Science and TechnologyShanghaiChina