Effect of the Ala234Asp replacement in mitochondrial branched-chain amino acid aminotransferase on the production of BCAAs and fusel alcohols in yeast

Abstract

In the yeast Saccharomyces cerevisiae, the mitochondrial branched-chain amino acid (BCAA) aminotransferase Bat1 plays an important role in the synthesis of BCAAs (valine, leucine and isoleucine). Our upcoming study [Large et al. 2020

An overview of branched-chain amino acid aminotransferases: functional differences between mitochondrial and cytosolic isozymes in yeast and human

“…These opposite phenomena are potentially caused by the functional differences between Bat1 and Bat2, such as regulation of the BAT1 and BAT2 gene expression, expression of the BAT1 and BAT2 genes in different status of cell growth or nutrients, and localization of the Bat1 and Bat2 enzymes, all of which were mentioned above (Colón et al 2011;Eden et al 1996;González et al 2017;Hammer and Avalos 2017;Kispal et al 1996;Takpho et al 2018). Our recent study also showed the relevance for the effect of intracellular BCAA contents on the production levels of fusel alcohols by using the bat1Δ strain (Koonthongkaew et al 2020). Interestingly, the differences between the localization of Bat1 and that of Bat2 were consistent with the places where BCAA biosynthesis and the Ehrlich degradation of BCAAs in cells mainly occur.…”

“…Many findings concerning the physiological functions of Bat1 have been obtained from investigations performed to improve fusel alcohol production, especially with isobutanol, by utilizing yeast strains. Several studies have demonstrated an increase in the production level of isobutanol by deletion of the BAT1 gene (Park et al 2014;Hammer and Avalos 2017;Koonthongkaew et al 2020). Meanwhile, other studies have indicated a decrease (Ofuonye et al 2013) or no significant impact (Eden et al 2001;Zhang et al 2016) in isobutanol production levels by the deletion of the BAT1 gene.…”

“…Carbon source content in medium affects the expression level of Bat1 (Saerens et al 2008). Moreover, Bat1 contributed to the enhancement of the fermentation ability of S. cerevisiae under a high concentration of glucose in the medium (Koonthongkaew et al 2020). Overexpression of Bat1 increases the production level of short branched-chain fatty acids (C4-6) (Yu et al 2016).…”

“…However, few BCAT variants in these organisms have been identified or studied. We found that the dysfunctional variant of Bat1 (A234D) can enhance the production of fusel alcohol, an important flavor compound in alcoholic beverages (Koonthongkaew et al 2020). This mutation was originally from an industrial beer yeast strain, Wyeast 1056, which natively has a variant causing one amino acid substitution of A234D in Bat1 on one of the four chromosomes (Large et al 2020).…”

“…Because they have the same catalytic function, which is to drive the transamination reaction, the physiological functions and regulatory mechanisms of BCATs have not attracted the attentions of researchers. However, recent studies clarified the importance of human BCATs and yeast BCATs in the progression of many kinds of cancers (Ananieva and Wilkinson 2018) and the production of higher alcohol (Zhang et al 2016;Hammer and Avalos 2017;Koonthongkaew et al 2020), respectively. Moreover, many studies indicated differences in non-catalytic functions between mitochondrial and cytosolic BCATs, such as the regulatory mechanisms underlying BCAT expression and the interaction between BCAT and other proteins in the cell (Costanzo et al 2016;Kingsbury et al 2015;Lorenzil et al 2016;Yu et al 20162016).…”