How a methanogen assimilates sulfate: Structural and functional elucidation of the complete sulfate-reduction pathway

Jespersen, M.; Wagner, T.

doi:10.1101/2022.10.18.512691

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bioRxiv · 10.1101/2022.10.18.512691

How a methanogen assimilates sulfate: Structural and functional elucidation of the complete sulfate-reduction pathway

Jespersen, M.·Wagner, T.

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Abstract

By growing on sulfate as the sole source of sulfur, Methanothermococcus thermolithotrophicus breaks a dogma: the ancient metabolic pathways methanogenesis and sulfate-reduction should not co-occur in one organism due to toxic intermediates and energetic barriers. Using a complementary approach of physiological, biochemical, and structural studies, we provide a snapshot of the complete sulfate-reduction pathway of the methanogenic archaeon. While the first two reactions proceed via an ATP-sulfurylase and APS-kinase, common to other organisms, the further steps are catalysed by non-canonical enzymes. 3-phosphoadenosine-5-phosphosulfate (PAPS) released by the APS-kinase is converted into sulfite and 3-phosphoadenosine-5-phosphate (PAP) by a new class of PAPS-reductase that shares high similarity with the APS-reductases involved in dissimilatory sulfate-reduction. The generated PAP is efficiently hydrolysed by a PAP-phosphatase that was likely derived from an RNA exonuclease. Finally, the F420-dependent sulfite-reductase converts sulfite to sulfide for cellular assimilation. While metagenomic and metatranscriptomic studies suggest that genes of the sulfate-reduction pathway are present in various methanogens, M. thermolithotrophicus uses a distinct way to assimilate sulfate. We propose that its entire sulfate-assimilation pathway was derived from a "mix-and-match" strategy in which the methanogen acquired assimilatory and dissimilatory enzymes from other microorganisms and shaped them to fit its physiological needs.

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Jespersen, M., Wagner, T.. 2022-10-18. How a methanogen assimilates sulfate: Structural and functional elucidation of the complete sulfate-reduction pathway. https://doi.org/10.1101/2022.10.18.512691

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