Metabolic engineering of oleaginous yeast Rhodotorula toruloides for overproduction of triacetic acid lactone.

Autor: Cao M; Department of Chemical and Biomolecular Engineering, US Department of Energy Center for Bioenergy and Bioproducts Innovation (CABBI), Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA., Tran VG; Department of Chemical and Biomolecular Engineering, US Department of Energy Center for Bioenergy and Bioproducts Innovation (CABBI), Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA., Qin J; Department of Chemical Engineering, University of Massachusetts-Lowell, Lowell, Massachusetts, USA., Olson A; Department of Chemical Engineering, University of Massachusetts-Lowell, Lowell, Massachusetts, USA., Mishra S; Department of Chemical and Biomolecular Engineering, US Department of Energy Center for Bioenergy and Bioproducts Innovation (CABBI), Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA., Schultz JC; Department of Chemical and Biomolecular Engineering, US Department of Energy Center for Bioenergy and Bioproducts Innovation (CABBI), Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA., Huang C; Department of Chemical and Biomolecular Engineering, US Department of Energy Center for Bioenergy and Bioproducts Innovation (CABBI), Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA., Xie D; Department of Chemical Engineering, University of Massachusetts-Lowell, Lowell, Massachusetts, USA., Zhao H; Department of Chemical and Biomolecular Engineering, US Department of Energy Center for Bioenergy and Bioproducts Innovation (CABBI), Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.; Departments of Chemistry, Biochemistry, and Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Jazyk: angličtina
Zdroj: Biotechnology and bioengineering [Biotechnol Bioeng] 2022 Sep; Vol. 119 (9), pp. 2529-2540. Date of Electronic Publication: 2022 Jun 23.
DOI: 10.1002/bit.28159
Abstrakt: 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 ATP-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 or 23 g/L TAL, respectively. This study demonstrates that R. toruloides is a promising host for the production of TAL and other acetyl-CoA-derived polyketides from low-cost carbon sources.
(© 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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