Publications

• Novel proteins for homocysteine biosynthesis in anaerobic microorganisms.

  Rauch B.J., Gustafson A., Perona J.J.

  The metabolic network for sulfide assimilation and trafficking in methanogens is largely unknown. To discover novel proteins required for these processes, we used bioinformatics to identify genes co-occurring with the protein biosynthesis enzyme SepCysS, which converts phosphoseryl-tRNA(Cys) to cy ... >> More

  The metabolic network for sulfide assimilation and trafficking in methanogens is largely unknown. To discover novel proteins required for these processes, we used bioinformatics to identify genes co-occurring with the protein biosynthesis enzyme SepCysS, which converts phosphoseryl-tRNA(Cys) to cysteinyl-tRNA(Cys) in nearly all methanogens. Exhaustive analysis revealed three conserved protein families, each containing molecular signatures predicting function in sulfur metabolism. One of these families, classified within clusters of orthologous groups (COG) 1900, possesses two conserved cysteine residues and is often found in genomic contexts together with known sulfur metabolic genes. A second protein family is predicted to bind two 4Fe-4S clusters. All three genes were also identified in more than 50 strictly anaerobic bacterial genera from nine distinct phyla. Gene-deletion and growth experiments in Methanosarcina acetivorans, using sulfide as the sole sulfur source, demonstrate that two of the proteins (MA1821 and MA1822) are essential to homocysteine biosynthesis in a background lacking an additional gene for sulfur insertion into homocysteine. Mutational analysis confirms the importance of several structural elements, including a conserved cysteine residue and the predicted 4Fe-4S cluster-binding domain. << Less

  Mol. Microbiol. 94:1330-1342(2014) [PubMed] [EuropePMC]

• Homocysteine is biosynthesized from aspartate semialdehyde and hydrogen sulfide in methanogenic archaea.

  Allen K.D., Miller D.V., Rauch B.J., Perona J.J., White R.H.

  The biosynthetic route for homocysteine, intermediate in methionine biosynthesis, is unknown in some methanogenic archaea because homologues of the canonical required genes cannot be identified. Here we demonstrate that Methanocaldococcus jannaschii can biosynthesize homocysteine from aspartate se ... >> More

  The biosynthetic route for homocysteine, intermediate in methionine biosynthesis, is unknown in some methanogenic archaea because homologues of the canonical required genes cannot be identified. Here we demonstrate that Methanocaldococcus jannaschii can biosynthesize homocysteine from aspartate semialdehyde and hydrogen sulfide. Additionally, we confirm the genes involved in this new pathway in Methanosarcina acetivorans. A possible series of reactions in which a thioaldehyde is formed and then reduced to a thiol are proposed. This represents a novel route for the biosynthesis of homocysteine and exemplifies unique aspects of sulfur chemistry occurring in prebiotic environments and in early life forms. << Less

  Biochemistry 54:3129-3132(2015) [PubMed] [EuropePMC]