title: Discovery of a substrate selectivity motif in amino acid decarboxylases unveils a taurine biosynthesis pathway in prokaryotes.
abstract: Taurine, the most abundant free amino acid in mammals, with many critical roles such as neuronal development, had so far only been reported to be synthetized in eukaryotes. Taurine is the major product of cysteine metabolism in mammals, and its biosynthetic pathway consists of cysteine dioxygenase and cysteine sulfinic acid decarboxylase (hCSAD). Sequence, structural, and mutational analyses of the structurally and sequentially related hCSAD and human glutamic acid decarboxylase (hGAD) enzymes revealed a three residue substrate recognition motif (X1aa19X2aaX3), within the active site that is responsible for coordinating their respective preferred amino acid substrates. Introduction of the cysteine sulfinic acid (CSA) motif into hGAD (hGAD-S192F/N212S/F214Y) resulted in an enzyme with a >700 fold switch in selectivity toward the decarboxylation of CSA over its preferred substrate, l-glutamic acid. Surprisingly, we found this CSA recognition motif in the genome sequences of several marine bacteria, prompting us to evaluate the catalytic properties of bacterial amino acid decarboxylases that were predicted by sequence motif to decarboxylate CSA but had been annotated as GAD enzymes. We show that CSAD from Synechococcus sp. PCC 7335 specifically decarboxylated CSA and that the bacteria accumulated intracellular taurine. The fact that CSAD homologues exist in certain bacteria and are frequently found in operons containing the recently discovered bacterial cysteine dioxygenases that oxidize l-cysteine to CSA supports the idea that a bona fide bacterial taurine biosynthetic pathway exists in prokaryotes.
authors: Departments of Biomedical and Chemical Engineering, ‡Section of Molecular Genetics and Microbiology and §Institute for Cellular and Molecular Biology, University of Texas , Austin, Texas 78712, United States.
authors: Giulia
authors: G
authors: Agnello
authors: Leslie L
authors: LL
authors: Chang
authors: Candice M
authors: CM
authors: Lamb
authors: George
authors: G
authors: Georgiou
authors: Everett M
authors: EM
authors: Stone
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology*; D002262:Carboxy-Lyases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D055808:Drug Discovery; D004795:Enzyme Stability; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D015398:Signal Transduction; D013379:Substrate Specificity; D013654:Taurine / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
chemical_list: D013654:Taurine; D002262:Carboxy-Lyases; C019972:sulfoalanine decarboxylase
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