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Biosynthesis of geranate via isopentenol utilization pathway in Escherichia coli
  • +3
  • Qiuchi Pan,
  • Xiaoqiang Ma,
  • Hong Liang,
  • Yurou Liu,
  • Greg Stephanopoulos,
  • Kang Zhou
Qiuchi Pan
Singapore-MIT Alliance for Research and Technology Centre

Corresponding Author:pan_qiuchi@u.nus.edu

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Xiaoqiang Ma
Singapore-MIT Alliance for Research and Technology Centre
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Hong Liang
Singapore-MIT Alliance for Research and Technology Centre
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Yurou Liu
Singapore-MIT Alliance for Research and Technology Centre
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Greg Stephanopoulos
Singapore-MIT Alliance for Research and Technology Centre
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Kang Zhou
Singapore-MIT Alliance for Research and Technology Centre
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Abstract

Isoprenoids are a large family of natural products with diverse structures, which allow them to play diverse and important roles in the physiology of plants and animals. They also have important commercial uses as pharmaceuticals, flavouring agents, fragrances, and nutritional supplements. Recently, metabolic engineering has been intensively investigated and emerged as the technology of choice for the production of isoprenoids through microbial fermentation. Isoprenoid biosynthesis typically originates in plants from acetyl-coA in central carbon metabolism, however, a recent study reported an alternative pathway, the Isopentenol Utilization pathway (IUP), that can provide the building blocks of isoprenoid biosynthesis from affordable C5 substrates. In this work, we expressed the IUP in Escherichia coli to efficiently convert isopentenols into geranate, a valuable isoprenoid compound. We first established a geraniol-producing strain in E. coli that uses the IUP. Then, we extended the geraniol synthesis pathway to produce geranate through two oxidation reactions catalysed by two alcohol/aldehyde dehydrogenases from Castellaniella defragrans. The geranate titer was further increased by optimizing the expression of the two dehydrogenases and also parameters of the fermentation process. The best strain produced 764 mg/L geranate in 24 h from 2 g/L isopentenols (a mixture of isoprenol and prenol). We also investigated if the dehydrogenases could accept other isoprenoid alcohols as substrates.
07 Jul 2022Submitted to Biotechnology and Bioengineering
07 Jul 2022Submission Checks Completed
07 Jul 2022Assigned to Editor
10 Jul 2022Reviewer(s) Assigned
28 Jul 2022Review(s) Completed, Editorial Evaluation Pending
28 Jul 2022Editorial Decision: Revise Major
03 Oct 20221st Revision Received
05 Oct 2022Submission Checks Completed
05 Oct 2022Assigned to Editor
06 Oct 2022Reviewer(s) Assigned
08 Oct 2022Review(s) Completed, Editorial Evaluation Pending
08 Oct 2022Editorial Decision: Accept
Jan 2023Published in Biotechnology and Bioengineering volume 120 issue 1 on pages 230-238. 10.1002/bit.28255