AUTHOR=Gu Zhongkai , Sun Yufan , Wu Feizhen , Wu Xiaomo 

TITLE=Mechanism of Growth Regulation of Yeast Involving Hydrogen Sulfide From S-Propargyl-Cysteine Catalyzed by Cystathionine-γ-Lyase

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.679563

DOI=10.3389/fmicb.2021.679563

ISSN=1664-302X

ABSTRACT=<p>Pathogenic fungi are recognized as a progressive threat to humans, particularly those with the immunocompromised condition. The growth of fungi is controlled by several factors, one of which is signaling molecules, such as hydrogen sulfide (H<sub>2</sub>S), which was traditionally regarded as a toxic gas without physiological function. However, recent studies have revealed that H<sub>2</sub>S is produced enzymatically and endogenously in several species, where it serves as a gaseous signaling molecule performing a variety of critical biological functions. However, the influence of this endogenous H<sub>2</sub>S on the biological activities occurring within the pathogenic fungi, such as transcriptomic and phenotypic alternations, has not been elucidated so far. Therefore, the present study was aimed to decipher this concern by utilizing <italic>S</italic>-propargyl-cysteine (SPRC) as a novel and stable donor of H<sub>2</sub>S and <italic>Saccharomyces cerevisiae</italic> as a fungal model. The results revealed that the yeast could produce H<sub>2</sub>S by catabolizing SPRC, which facilitated the growth of the yeast cells. This implies that the additional intracellularly generated H<sub>2</sub>S is generated primarily from the enhanced sulfur-amino-acid-biosynthesis pathways and serves to increase the growth rate of the yeast, and presumably the growth of the other fungi as well. In addition, by deciphering the implicated pathways and analyzing the <italic>in vitro</italic> enzymatic activities, cystathionine-γ-lyase (<italic>CYS3</italic>) was identified as the enzyme responsible for catabolizing SPRC into H<sub>2</sub>S in the yeast, which suggested that cystathionine-γ-lyase might play a significant role in the regulation of H<sub>2</sub>S-related transcriptomic and phenotypic alterations occurring in yeast. These findings provide important information regarding the mechanism underlying the influence of the gaseous signaling molecules such as H<sub>2</sub>S on fungal growth. In addition, the findings provide a better insight to the <italic>in vivo</italic> metabolism of H<sub>2</sub>S-related drugs, which would be useful for the future development of anti-fungal drugs.</p>