Activation of Haa1 and War1 transcription factors by differential binding of weak acid anions in Saccharomyces cerevisiae.

Myung Sup Kim,Kwang Hyun Park,Kyung Hee Cho,Ji-Sook Hahn,Jyongsik Jang

doi:10.1093/nar/gky1188

Abstract

In Saccharomyces cerevisiae, Haa1 and War1 transcription factors are involved in cellular adaptation against hydrophilic weak acids and lipophilic weak acids, respectively. However, it is unclear how these transcription factors are differentially activated depending on the identity of the weak acid. Using a field-effect transistor (FET)-type biosensor based on carbon nanofibers, in the present study we demonstrate that Haa1 and War1 directly bind to various weak acid anions with different affinities. Haa1 is most sensitive to acetate, followed by lactate, whereas War1 is most sensitive to benzoate, followed by sorbate, reflecting their differential activation during weak acid stresses. We show that DNA binding by Haa1 is induced in the presence of acetic acid and that the N-terminal Zn-binding domain is essential for this activity. Acetate binds to the N-terminal 150-residue region, and the transcriptional activation domain is located between amino acid residues 230 and 483. Our data suggest that acetate binding converts an inactive Haa1 to the active form, which is capable of DNA binding and transcriptional activation.

Highlights

Weak monocarboxylic acids such as acetic, propionic, sorbic and benzoic acid are widely used food and beverage preservatives that prevent microbial cell growth [1,2,3]
The N-terminal region of Haa1 is homologous to the DNAbinding domain of Cu-activated transcription factor Ace1, which consists of Zn-binding and Cu-binding domains (Figure 1A)
Because Haa1 is not regulated by Cu [28], we investigated the role of the Haa1 Zn-binding domain

Summary

Introduction

Weak monocarboxylic acids such as acetic, propionic, sorbic and benzoic acid are widely used food and beverage preservatives that prevent microbial cell growth [1,2,3]. Acetic acid and other weak acids present in lignocellulosic hydrolysates prevent the efficient utilization of lignocellulosic biomass [4,5,6]. Saccharomyces cerevisiae, which has served as an important model for studies on the responses of yeast to weak acids, is a promising host for the production of valuable chemicals including lactic acid [8]. Understanding the mechanisms by which yeasts resist weak acids is important for the control of spoilage yeasts that are resistant to weak acid preservatives, and for the generation of robust industrial yeast strains for the production of valuable chemicals

Methods

Results

Conclusion