Applied Microbiology and Biotechnology

, Volume 102, Issue 18, pp 7759–7773 | Cite as

Metabolic engineering strategies for enhanced shikimate biosynthesis: current scenario and future developments

  • Muhammad Bilal
  • Songwei Wang
  • Hafiz M. N. Iqbal
  • Yuping Zhao
  • Hongbo HuEmail author
  • Wei Wang
  • Xuehong Zhang


Shikimic acid is an important intermediate for the manufacture of the antiviral drug oseltamivir (Tamiflu®) and many other pharmaceutical compounds. Much of its existing supply is obtained from the seeds of Chinese star anise (Illicium verum). Nevertheless, plants cannot supply a stable source of affordable shikimate along with laborious and cost-expensive extraction and purification process. Microbial biosynthesis of shikimate through metabolic engineering and synthetic biology approaches represents a sustainable, cost-efficient, and environmentally friendly route than plant-based methods. Metabolic engineering allows elevated shikimate production titer by inactivating the competing pathways, increasing intracellular level of key precursors, and overexpressing rate-limiting enzymes. The development of synthetic and systems biology-based novel technologies have revealed a new roadmap for the construction of high shikimate-producing strains. This review elaborates the enhanced biosynthesis of shikimate by utilizing an array of traditional metabolic engineering along with novel advanced technologies. The first part of the review is focused on the mechanistic pathway for shikimate production, use of recombinant and engineered strains, improving metabolic flux through the shikimate pathway, chemically inducible chromosomal evolution, and bioprocess engineering strategies. The second part discusses a variety of industrially pertinent compounds derived from shikimate with special reference to aromatic amino acids and phenazine compound, and main engineering strategies for their production in diverse bacterial strains. Towards the end, the work is wrapped up with concluding remarks and future considerations.


Shikimic acid Metabolic engineering Systems biotechnology Bioprocess engineering Shikimate-derived compounds Biological functionalities 


Funding information

This work was supported by the National Natural Science Foundation of China (No. 31670033).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Muhammad Bilal
    • 1
    • 2
  • Songwei Wang
    • 1
  • Hafiz M. N. Iqbal
    • 3
  • Yuping Zhao
    • 2
  • Hongbo Hu
    • 1
    • 4
    Email author
  • Wei Wang
    • 1
  • Xuehong Zhang
    • 1
  1. 1.State Key Laboratory of Microbial Metabolism, School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina
  2. 2.School of Life Science and Food EngineeringHuaiyin Institute of TechnologyHuaianChina
  3. 3.Tecnologico de MonterreySchool of Engineering and Sciences, Campus MonterreyMonterreyMexico
  4. 4.National Experimental Teaching Center for Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina

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