Ethanol represses the expression of methanol-inducible genes via acetyl-CoA synthesis in the yeast Komagataella phaffii.

Sci Rep

Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto, 606-8502, Japan.

Published: December 2018

AI Article Synopsis

  • In methylotrophic yeasts like Komagataella phaffii, ethanol can suppress the expression of genes normally activated by methanol, a process known as ethanol repression.
  • The study revealed that the conversion of ethanol into acetyl-CoA, involving several enzymes including acetyl-CoA synthetase (ACS), plays a key role in this repression mechanism.
  • The findings highlight that parts of the ACS enzyme, particularly the conserved N-terminal motif, are essential for ethanol repression, along with the phosphorylation of a transcription factor and the regulation of ACS activity through autophagy during methanol-induced gene expression.

Article Abstract

In methylotrophic yeasts, the expression of methanol-inducible genes is repressed by ethanol even in the presence of methanol, a phenomenon called ethanol repression. The mechanism of ethanol repression in Komagataella phaffii (Pichia pastoris) was studied, and acetyl-CoA synthesis from ethanol by sequential reactions of alcohol dehydrogenase, aldehyde dehydrogenase and acetyl-CoA synthetase (ACS) was involved in ethanol repression. Molecular analysis of the ACS-encoding gene product KpAcs1 revealed that its N-terminal motif, which is conserved in methylotrophic yeasts, was required for ethanol repression. ACS activity was downregulated during methanol-induced gene expression, which partially depended on autophagy. In addition, acetyl-CoA synthesis and phosphorylation of a transcription factor KpMxr1 were found to contribute to ethanol repression in a synergistic manner.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303403PMC
http://dx.doi.org/10.1038/s41598-018-36732-2DOI Listing

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