Production of triacetic acid lactone from oleic acid by engineering the yeast Candida viswanathii

Saptarshi Ghosh; Alex Hutagalung; Yuqian Gao; Javier E Flores; Yichao Han; Joonhoon Kim; Meagan C Burnet; Young-Mo Kim; Alberto Rodriguez

doi:10.1186/s12934-025-02841-7

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Production of triacetic acid lactone from oleic acid by engineering the yeast Candida viswanathii

Journal article

Open access

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Production of triacetic acid lactone from oleic acid by engineering the yeast Candida viswanathii

Saptarshi Ghosh, Alex Hutagalung, Yuqian Gao, Javier E Flores, Yichao Han, Joonhoon Kim, Meagan C Burnet, Young-Mo Kim and Alberto Rodriguez

Microbial cell factories, Vol.24(1), pp.215-13

10/06/2025

DOI: 10.1186/s12934-025-02841-7

PMCID: PMC12502205

PMID: 41053888

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https://doi.org/10.1186/s12934-025-02841-7View

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Abstract

Triacetic acid lactone (TAL) is a promising platform chemical to produce valuable compounds. The development of engineered microbial hosts to efficiently produce TAL from lipid-containing waste streams could be a cost-effective, sustainable and environmentally friendly approach to meet the industrial demand. In this study, we engineered the yeast Candida viswanathii, possessing robust fatty acid conversion capabilities, to develop an alternative route for TAL production from fatty acids that aims to maximize conversion of the acetyl-CoA pool generated by β-oxidation in the peroxisome. To do so, we inactivated the carnitine acetyltransferase gene to block the transport of acetyl-CoA out of the peroxisome and overexpressed the enzymes methylmalonyl-CoA carboxyltransferase, 2-pyrone synthase and pyruvate carboxylase in the peroxisome to convert acetyl-CoA into TAL. We also performed an adaptive laboratory evolution experiment to obtain mutants with higher growth rate in medium with oleic acid and observed marked differences in central carbon metabolism and organic acid production pathways between the evolved and parental strains. These strains were further engineered by integrating additional copies of TAL biosynthetic genes while reducing competing reactions like ω-oxidation and Lipid biosynthesis, resulting in up to 50-fold increase in titers relative to the initial strain, reaching 280 mg/L. This study contributes to the development of bioprocesses that valorize fatty acids as microbial conversion substrates for the production of valuable compounds.

Acetyl Coenzyme A - metabolism

Candida - genetics

Candida - metabolism

Lactones - metabolism

Metabolic Engineering

Oleic Acid - metabolism

Peroxisomes - metabolism

Pyrones

Details

Title: Subtitle: Production of triacetic acid lactone from oleic acid by engineering the yeast Candida viswanathii
Creators: Saptarshi Ghosh - Sandia National Laboratories
Alex Hutagalung - Pyrone Systems Inc, San Diego, CA, 92130, USA
Yuqian Gao - Pacific Northwest National Laboratory
Javier E Flores - Pacific Northwest National Laboratory
Yichao Han - Pacific Northwest National Laboratory
Joonhoon Kim - Pacific Northwest National Laboratory
Meagan C Burnet - Pacific Northwest National Laboratory
Young-Mo Kim - Pacific Northwest National Laboratory
Alberto Rodriguez - Sandia National Laboratories California
Resource Type: Journal article
Publication Details: Microbial cell factories, Vol.24(1), pp.215-13
DOI: 10.1186/s12934-025-02841-7
PMID: 41053888
PMCID: PMC12502205
NLM abbreviation: Microb Cell Fact
ISSN: 1475-2859
eISSN: 1475-2859
Grant note: DE-AC02-05CH11231 / Bioenergy Technologies Office
Language: English
Date published: 10/06/2025
Academic Unit: Biostatistics
Record Identifier: 9985112969102771

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