The Francis Crick Institute
journal.pbio.3001912 (1).pdf (2.74 MB)

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

Download (2.74 MB)
journal contribution
posted on 2022-12-21, 12:22 authored by Jason SL Yu, Benjamin M Heineike, Johannes Hartl, Simran K Aulakh, Clara Correia-Melo, Andrea Lehmann, Oliver Lemke, Federica Agostini, Cory T Lee, Vadim Demichev, Christoph B Messner, Michael Mülleder, Markus Ralser
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.


Crick (Grant ID: 10134, Grant title: Ralser FC001134) Wellcome Trust (Grant ID: 200829/Z/16/Z, Grant title: WT 200829/Z/16/Z)