Inorganic sulfur fixation via a new homocysteine synthase allows yeast cells to cooperatively compensate for methionine auxotrophy

Abstract

The assimilation, incorporation, and metabolism of sulfur is a fundamental process across all domains of life, yet how cells deal with varying sulfur availability is not well understood. We studied an unresolved conundrum of sulfur fixation in yeast, in which organosulfur auxotrophy caused by deletion of the homocysteine synthase Met17p is overcome when cells are inoculated at high cell density. In combining the use of self-establishing metabolically cooperating (SeMeCo) communities with proteomic, genetic, and biochemical approaches, we discovered an uncharacterized gene product YLL058Wp, herein named Hydrogen Sulfide Utilizing-1 (HSU1). Hsu1p acts as a homocysteine synthase and allows the cells to substitute for Met17p by reassimilating hydrosulfide ions leaked from met17Δ cells into O-acetyl-homoserine and forming homocysteine. Our results show that cells can cooperate to achieve sulfur fixation, indicating that the collective properties of microbial communities facilitate their basic metabolic capacity to overcome sulfur limitation.

When is an auxotroph not an auxotroph: how budding yeast lackingMET17collectively overcome their metabolic defect

“…This indicated that we were not merely observing residual growth fueled by organosulfurs that the cells had accumulated during exponential growth in methionine-supplemented medium. Similar observations have since been reported by other labs [24,25], and chromatographic analyses has confirmed that organosulfur contaminants occur in negligible quantities in the commercially available yeast nitrogenous base that was used to prepare SD medium [25].…”

“…Indeed, while met17∆ grew in a density-dependent fashion ( indicating that the inability of met17∆yll058w∆ to grow on sulfate did not result from impairments in sulfide release but from defects in sulfide assimilation. While we were investigating this phenomenon, two other groups simultaneously reported this sulfide-assimilation function of YLL058W [24,25], and Yu et.al. named the locus Hydrogen Sulfide Utilizing-1 (HSU1) [25].…”

“…While we were investigating this phenomenon, two other groups simultaneously reported this sulfide-assimilation function of YLL058W [24,25], and Yu et.al. named the locus Hydrogen Sulfide Utilizing-1 (HSU1) [25]. We will henceforth use the name HSU1 to refer to YLL058W.…”

“…We will henceforth use the name HSU1 to refer to YLL058W. These other groups additionally demonstrated that Hsu1 protein can catalyze the same biochemical reaction as MET17, albeit at considerably lower efficiency [24,25].…”

Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan

“…Furthermore, endogenous hydrogen sulfide (H 2 S) production, as part of the organic sulfur cycle, 79 is essential for the beneficial effects of dietary restriction 80 and has been shown to provide health benefits in experimental organisms, ranging from protection from ischemia/reperfusion injury to lifespan extension. 81 In yeast, H 2 S extends CLS in a temporally resolved manner, 82 and a recent study in our lab found that MET15 auxotrophs generate increased levels of H 2 S, 83 hence it is possible that increased levels of H 2 S also occur in SeMeCo and participate in the protective role of the self-generated exometabolome.…”