title: Heterologous production of polyunsaturated fatty acids in Saccharomyces cerevisiae causes a global transcriptional response resulting in reduced proteasomal activity and increased oxidative stress.
abstract: Due to their health benefits there is much interest in developing microbial processes for efficient production of polyunsaturated fatty acids (PUFAs). In this study we co-expressed Mucor rouxii Δ(12) - and Δ(6) -desaturase genes in Saccharomyces cerevisiae, which resulted in a yeast strain that accumulated linoleic acid and γ-linolenic acid in the different lipid species. Additionally, the strain contained higher levels of phospholipids and lower levels of ergosterol than the reference strain. Integrated analysis of the transcriptome revealed decreased expression of genes involved in ergosterol biosynthesis, but more unexpectedly it also pointed towards attenuated activity of the ubiquitin-proteasome system and a reduced oxidative stress response. In vitro and in vivo measurements showed reduced levels of all three proteasomal activities and also increased levels of reactive oxidative species in the PUFA-producing strain. Overall our results clearly show that PUFAs in yeast can be detrimental for several key cellular pathways, such as the oxidative stress response and proteasomal activity, suggesting that the membrane composition is of vital importance for these processes.
authors.affiliation: School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, Thailand.
authors.forename: Rawisara
authors.initials: R
authors.lastname: Ruenwai
authors.forename: Andrea
authors.initials: A
authors.lastname: Neiss
authors.forename: Kobkul
authors.initials: K
authors.lastname: Laoteng
authors.forename: Wanwipa
authors.initials: W
authors.lastname: Vongsangnak
authors.forename: Arastoo Badoei
authors.initials: AB
authors.lastname: Dalfard
authors.forename: Supapon
authors.initials: S
authors.lastname: Cheevadhanarak
authors.forename: Dina
authors.initials: D
authors.lastname: Petranovic
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D004875:Ergosterol / Q000032:analysis / Q000302:isolation & purification; D044943:Fatty Acid Desaturases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D009090:Mucorales / Q000235:genetics / Q000378:metabolism; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated; D044943:Fatty Acid Desaturases; D046988:Proteasome Endopeptidase Complex; D004875:Ergosterol