Dynamic analysis of the KlGAL regulatory system in Kluyveromyces lactis: a comparative study with Saccharomyces cerevisiae

Abstract

The GAL regulatory system is highly conserved in yeast species of Saccharomyces cerevisiae and Kluyveromyces lactis. While the GAL system is a well studied system in S. cerevisiae, the dynamic behavior of the KlGAL system in K. lactis has not been characterized. Here, we have characterized the GAL system in yeast K. lactis by developing a dynamic model and comparing its performance to its not-sodistant cousin S. cerevisiae. The present analysis demonstrates the significance of the autoregulatory feedbacks due to KlGal4p, KlGal80p, KlGal1p and Lac12p on the dynamic performance of the KlGAL switch. The model predicts the experimentally observed absence of bistability in the wild type strain of K. lactis, unlike the short term memory of preculturing conditions observed in S. cerevisiae. The performance of the GAL switch is distinct for the two yeast species although they share similarities in the molecular components. The analysis suggests that the whole genome duplication of S. cerevisiae, which resulted in a dedicated inducer protein, Gal3p, may be responsible for the high sensitivity of the system to galactose concentrations. On the other hand, K. lactis uses a bifunctional protein as an inducer in addition to its galactokinase activity, which restricts its regulatory role and hence higher galactose levels in the medium are needed to trigger the GAL system.

Yeast on the milky way: genetics, physiology and biotechnology of Kluyveromyces lactis

“…KlGal1 is a bifunctional protein, which in addition to its kinase activity acts as an inducer of genes involved in lactose utilization. This is achieved by its interaction with KlGal80, which relieves the inhibitory function of the latter on the transcriptional activator Lac9, the K. lactis Gal4 homologue (Figure ) (see Anders et al ., ; Pannala et al ., and references therein). In this context, LAC9 gene expression is autoregulated, thus explaining the general effect of the KlMig1 repressor on lactose utilization.…”

Insights into molecular evolution from yeast genomics

“…Recently, several mechanisms of regulatory evolution have been characterized in the cell-type specification system (Baker et al, 2012;Booth et al, 2010) and the ribosomal transcriptional control network (Lavoie et al, 2010;Mallick and Whiteway, 2013). Along with the galactose (GAL) utilization network, which has revealed several surprising and important patterns of evolution (Hittinger et al, 2004;Martchenko et al, 2007;Hittinger and Carroll, 2007;Hittinger et al, 2010;Josephides and Moses, 2011;Pannala et al, 2011), these yeast regulatory networks are now among the best understood systems for regulatory network evolution.…”