Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Shikimate Metabolic Pathway Engineering in Corynebacterium glutamicum

  • Park, Eunhwi (Department of Biological Sciences and Bioengineering, Inha University) ;
  • Kim, Hye-Jin (Department of Biological Sciences and Bioengineering, Inha University) ;
  • Seo, Seung-Yeul (STR Biotech Co., Ltd.) ;
  • Lee, Han-Na (STR Biotech Co., Ltd.) ;
  • Choi, Si-Sun (Department of Biological Sciences and Bioengineering, Inha University) ;
  • Lee, Sang Joung (STR Biotech Co., Ltd.) ;
  • Kim, Eung-Soo (Department of Biological Sciences and Bioengineering, Inha University)
  • Received : 2021.06.04
  • Accepted : 2021.08.02
  • Published : 2021.09.28
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Abstract

Shikimate is a key high-demand metabolite for synthesizing valuable antiviral drugs, such as the anti-influenza drug, oseltamivir (Tamiflu). Microbial-based strategies for shikimate production have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. In this study, a microbial cell factory using Corynebacterium glutamicum was designed to overproduce shikimate in a fed-batch culture system. First, the shikimate kinase gene (aroK) responsible for converting shikimate to the next step was disrupted to facilitate the accumulation of shikimate. Several genes encoding the shikimate bypass route, such as dehydroshikimate dehydratase (QsuB), pyruvate kinase (Pyk1), and quinate/shikimate dehydrogenase (QsuD), were disrupted sequentially. An artificial operon containing several shikimate pathway genes, including aroE, aroB, aroF, and aroG were overexpressed to maximize the glucose uptake and intermediate flux. The rationally designed shikimate-overproducing C. glutamicum strain grown in an optimized medium produced approximately 37.3 g/l of shikimate in 7-L fed-batch fermentation. Overall, rational cell factory design and culture process optimization for the microbial-based production of shikimate will play a key role in complementing traditional plant-derived shikimate production processes.

Keywords

Acknowledgement

This work was carried out with the support of "Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ01563901)" Rural Development Administration, Republic of Korea and the National Research Foundation of Korea (NRF), and the Center for Women In Science, Engineering and Technology (WISET-2021-043) Grant funded by the Ministry of Science and ICT(MSIT) under the Program for Returners into R&D.

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