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Metabolic Engineering of Oleaginous Yeast Rhodotorula toruloides for Overproduction of Triacetic Acid Lactone
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  • Mingfeng Cao,
  • Vinh Tran,
  • Jiansong Qin,
  • Andrew Olson ,
  • John Schultz,
  • Chunshuai Huang,
  • DONGMING XIE,
  • Huimin Zhao
Mingfeng Cao
University of Illinois Urbana-Champaign Department of Chemical and Biomolecular Engineering

Corresponding Author:[email protected]

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Vinh Tran
University of Illinois Urbana-Champaign Department of Chemical and Biomolecular Engineering
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Jiansong Qin
University of Massachusetts Lowell
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Andrew Olson
University of Massachusetts Lowell
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John Schultz
University of Illinois Urbana-Champaign Department of Chemical and Biomolecular Engineering
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Chunshuai Huang
University of Illinois Urbana-Champaign Department of Chemical and Biomolecular Engineering
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DONGMING XIE
University of Massachusetts Lowell
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Huimin Zhao
University of Illinois Urbana-Champaign Department of Chemical and Biomolecular Engineering
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Abstract

The plant-sourced polyketide triacetic acid lactone (TAL) has been recognized as a promising platform chemical for the biorefinery industry. However, its practical application was rather limited due to low natural abundance and inefficient cell factories for biosynthesis. Here we report the metabolic engineering of oleaginous yeast Rhodotorula toruloides for TAL overproduction. We first introduced a 2-pyrone synthase gene from Gerbera hybrida ( GhPS) into R. toruloides and investigated the effects of different carbon sources on TAL production. We then systematically employed a variety of metabolic engineering strategies to increase the flux of acetyl-CoA by enhancing its biosynthetic pathways and disrupting its competing pathways. We found that overexpression of citrate lyase (ACL1) improved TAL production by 45% compared to the GhPS overexpressing strain, and additional overexpression of acetyl-CoA carboxylase (ACC1) further increased TAL production by 29%. Finally, we characterized the resulting strain I12- ACL1-ACC1 using fed-batch bioreactor fermentation in glucose or oilcane juice medium with acetate supplementation and achieved a titer of 28 g/L or 23 g/L TAL, respectively. This study demonstrates that R. toruloides is a promising host for production of TAL and other acetyl-CoA-derived polyketides from low-cost carbon sources.
22 Feb 2022Submitted to Biotechnology and Bioengineering
22 Feb 2022Submission Checks Completed
22 Feb 2022Assigned to Editor
27 Feb 2022Reviewer(s) Assigned
25 Mar 2022Review(s) Completed, Editorial Evaluation Pending
25 Mar 2022Editorial Decision: Revise Major
13 May 20221st Revision Received
23 May 2022Submission Checks Completed
23 May 2022Assigned to Editor
29 May 2022Reviewer(s) Assigned
13 Jun 2022Review(s) Completed, Editorial Evaluation Pending
13 Jun 2022Editorial Decision: Accept
Sep 2022Published in Biotechnology and Bioengineering volume 119 issue 9 on pages 2529-2540. 10.1002/bit.28159