{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:51:14Z","timestamp":1780325474259,"version":"3.54.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2013CB531603"],"award-info":[{"award-number":["2013CB531603"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats: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<jats:sub>2<\/jats:sub>S), which was traditionally regarded as a toxic gas without physiological function. However, recent studies have revealed that H<jats:sub>2<\/jats: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<jats:sub>2<\/jats: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 <jats:italic>S<\/jats:italic>-propargyl-cysteine (SPRC) as a novel and stable donor of H<jats:sub>2<\/jats:sub>S and <jats:italic>Saccharomyces cerevisiae<\/jats:italic> as a fungal model. The results revealed that the yeast could produce H<jats:sub>2<\/jats:sub>S by catabolizing SPRC, which facilitated the growth of the yeast cells. This implies that the additional intracellularly generated H<jats:sub>2<\/jats: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 <jats:italic>in vitro<\/jats:italic> enzymatic activities, cystathionine-\u03b3-lyase (<jats:italic>CYS3<\/jats:italic>) was identified as the enzyme responsible for catabolizing SPRC into H<jats:sub>2<\/jats:sub>S in the yeast, which suggested that cystathionine-\u03b3-lyase might play a significant role in the regulation of H<jats:sub>2<\/jats: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<jats:sub>2<\/jats:sub>S on fungal growth. In addition, the findings provide a better insight to the <jats:italic>in vivo<\/jats:italic> metabolism of H<jats:sub>2<\/jats:sub>S-related drugs, which would be useful for the future development of anti-fungal drugs.<\/jats:p>","DOI":"10.3389\/fmicb.2021.679563","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T06:37:18Z","timestamp":1625207838000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Mechanism of Growth Regulation of Yeast Involving Hydrogen Sulfide From S-Propargyl-Cysteine Catalyzed by Cystathionine-\u03b3-Lyase"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhongkai","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feizhen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1523\/jneurosci.16-03-01066.1996","article-title":"The possible role of hydrogen sulfide as an endogenous neuromodulator.","volume":"16","author":"Abe","year":"1996","journal-title":"J. Neurosci."},{"key":"B2","doi-asserted-by":"crossref","first-page":"W597","DOI":"10.1093\/nar\/gks400","article-title":"ExPASy: SIB bioinformatics resource portal.","volume":"40","author":"Artimo","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms8023","article-title":"Molecular mechanism for USP7-mediated DNMT1 stabilization by acetylation.","volume":"6","author":"Cheng","year":"2015","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1006\/jmbi.1996.0508","article-title":"Crystal structure of the pyridoxal-5\u2019-phosphate dependent cystathionine beta-lyase from Escherichia coli at 1.83 A.","volume":"262","author":"Clausen","year":"1996","journal-title":"J. Mol. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1111\/1574-6976.12060","article-title":"Budding yeast as a model organism to study the effects of age.","volume":"38","author":"Denoth Lippuner","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1006\/bbrc.1997.6878","article-title":"The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide.","volume":"237","author":"Hosoki","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1093\/femsyr\/fox058","article-title":"Hydrogen sulfide and its roles in Saccharomyces cerevisiae in a winemaking context.","volume":"17","author":"Huang","year":"2017","journal-title":"FEMS Yeast Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.","volume":"37","author":"Huang da","year":"","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.","volume":"4","author":"Huang da","year":"","journal-title":"Nat. Protoc."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2018.01172","article-title":"Hydrogen Sulfide: a Gaseous Molecule in Postharvest Freshness.","volume":"9","author":"Huo","year":"2018","journal-title":"Front. Plant Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1109\/tcbb.2016.2537326","article-title":"Autumn Algorithm-Computation of Hybridization Networks for Realistic Phylogenetic Trees.","volume":"15","author":"Huson","year":"2018","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-460","article-title":"Dendroscope: an interactive viewer for large phylogenetic trees.","volume":"8","author":"Huson","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1093\/sysbio\/sys062","article-title":"Dendroscope 3: an interactive tool for rooted phylogenetic trees and networks.","volume":"61","author":"Huson","year":"2012","journal-title":"Syst. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1096\/fj.04-1815fje","article-title":"Hydrogen sulfide protects neurons from oxidative stress.","volume":"18","author":"Kimura","year":"2004","journal-title":"FASEB J."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.FUNK-0014-2016","article-title":"Fungi that infect humans.","volume":"5","author":"K\u00f6hler","year":"2017","journal-title":"Microbiol. Spectr."},{"key":"B16","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1111\/j.1469-7580.2009.01092.x","article-title":"Cystathionine gamma-lyase expression during avian embryogenesis.","volume":"215","author":"Kr\u00fcck","year":"2009","journal-title":"J. Anat."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1096\/fj.04-3583fje","article-title":"Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse.","volume":"19","author":"Li","year":"2005","journal-title":"FASEB J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.freeradbiomed.2009.04.014","article-title":"GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat.","volume":"47","author":"Li","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"B19","doi-asserted-by":"crossref","first-page":"W580","DOI":"10.1093\/nar\/gkv279","article-title":"The EMBL-EBI bioinformatics web and programmatic tools framework.","volume":"43","author":"Li","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.tim.2006.08.003","article-title":"Hydrogen sulfide: clandestine microbial messenger?.","volume":"14","author":"Lloyd","year":"2006","journal-title":"Trends Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1590\/s0100-879x2012001000003","article-title":"Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2\/STAT3 survival pathway.","volume":"45","author":"Luan","year":"2012","journal-title":"Braz. J. Med. Biol. Res."},{"key":"B22","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1515\/BC.2003.043","article-title":"Determinants of enzymatic specificity in the Cys-Met-metabolism PLP-dependent enzymes family: crystal structure of cystathionine gamma-lyase from yeast and intrafamiliar structure comparison.","volume":"384","author":"Messerschmidt","year":"2003","journal-title":"Biol. Chem."},{"key":"B23","doi-asserted-by":"crossref","first-page":"W566","DOI":"10.1093\/nar\/gkv468","article-title":"ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap.","volume":"43","author":"Metsalu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/1574-6976.12048","article-title":"Yeast: a simple model system to study complex phenomena of aneuploidy.","volume":"38","author":"Mulla","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cca.2014.10.037","article-title":"Hydrogen sulfide in signaling pathways.","volume":"439","author":"Olas","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1093\/bioinformatics\/btm076","article-title":"COBALT: constraint-based alignment tool for multiple protein sequences.","volume":"23","author":"Papadopoulos","year":"2007","journal-title":"Bioinformatics"},{"key":"B28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nri2939","article-title":"Immunity to fungal infections.","volume":"11","author":"Romani","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks.","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega.","volume":"7","author":"Sievers","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B32","article-title":"New method for quantification of gasotransmitter hydrogen sulfide in biological matrices by LC-MS\/MS.","volume":"7","author":"Tan","year":"2017","journal-title":"Sci. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks.","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nat. Protoc."},{"key":"B34","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.chom.2015.11.002","article-title":"Meta- and Orthogonal Integration of Influenza \u201cOMICs\u201d Data Defines a Role for UBR4 in Virus Budding.","volume":"18","author":"Tripathi","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1093\/bioinformatics\/bty896","article-title":"TPMCalculator: one-step software to quantify mRNA abundance of genomic features.","volume":"35","author":"Vera Alvarez","year":"2018","journal-title":"Bioinformatics"},{"key":"B36","first-page":"1161","article-title":"[Chemobiology at happy hour: yeast as a model for pharmacological screening].","volume":"30","author":"Voisset","year":"2014","journal-title":"Med. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/fjc.0b013e3181ac8e12","article-title":"S-propargyl-cysteine protects both adult rat hearts and neonatal cardiomyocytes from ischemia\/hypoxia injury: the contribution of the hydrogen sulfide-mediated pathway.","volume":"54","author":"Wang","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2013a multiple sequence alignment editor and analysis workbench.","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4800","DOI":"10.1128\/jb.175.15.4800-4808.1993","article-title":"Cloning and bacterial expression of the CYS3 gene encoding cystathionine gamma-lyase of Saccharomyces cerevisiae and the physicochemical and enzymatic properties of the protein.","volume":"175","author":"Yamagata","year":"1993","journal-title":"J. Bacteriol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.cca.2014.07.012","article-title":"Hydrogen sulfide as a potent cardiovascular protective agent.","volume":"437","author":"Yu","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1021\/cb400090d","article-title":"Controllable hydrogen sulfide donors and their activity against myocardial ischemia-reperfusion injury.","volume":"8","author":"Zhao","year":"2013","journal-title":"ACS Chem. Biol."}],"updated-by":[{"DOI":"10.3389\/fmicb.2021.761240","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000}}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.679563\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:58:45Z","timestamp":1632531525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.679563\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,2]]},"references-count":41,"alternative-id":["10.3389\/fmicb.2021.679563"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.679563","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fmicb.2021.761240","asserted-by":"object"}]},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,2]]},"article-number":"679563"}}