Homocysteine is biosynthesized from aspartate semialdehyde and hydrogen sulfide in methanogenic archaea.
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.
†Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States.
Kylie D
KD
Allen
†Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States.
Danielle V
DV
Miller
‡Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239-3098, United States.
Benjamin J
BJ
Rauch
‡Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239-3098, United States.|§Department of Chemistry, Portland State University, 1719 Southwest 10th Avenue, Portland, Oregon 97201, United States.
John J
JJ
Perona
†Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States.
Robert H
RH
White
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D053898:Biosynthetic Pathways; D019766:Genes, Archaeal; D006710:Homocysteine / Q000096:biosynthesis*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D017017:Methanococcus / Q000235:genetics / Q000378:metabolism*
D006710:Homocysteine; D001224:Aspartic Acid; C006644:aspartic semialdehyde; D006862:Hydrogen Sulfide