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B6db references: 19761441.a

type Journal Article
authors Graham DE, Taylor SM, Wolf RZ, Namboori SC.
title Convergent evolution of coenzyme M biosynthesis in the Methanosarcinales: cysteate synthase evolved from an ancestral threonine synthase
journal Biochem J
sel selected
ui 19761441 a
year (2009)
volume 424
number 3
pages 467-78
abstract The euryarchaeon Methanosarcina acetivorans has no homologs of the first three enzymes that produce the essential methanogenic coenzyme M (2-mercaptoethanesulfonate) in Methanocaldococcus jannaschii. A single M. acetivorans gene was heterologously expressed to produce a functional sulfopyruvate decarboxylase protein, the fourth canonical enzyme in this biosynthetic pathway. An adjacent gene, at locus MA3297, encodes one of the organism's two threonine synthase homologs. When both paralogs from this organism were expressed in an E. coli threonine synthase mutant, the MA1610 gene complemented the thrC mutation, while the MA3297 gene did not. Both pyridoxal 5'-phosphate-dependent proteins were heterologously expressed and purified, but only the MA1610 protein catalyzed the canonical threonine synthase reaction. The MA3297 protein specifically catalyzed a new beta-replacement reaction that converted L-phosphoserine and sulfite to L-cysteate and inorganic phosphate. This oxygen-independent mode of sulfonate biosynthesis exploits the facile nucleophilic addition of sulfite to an alpha,beta-unsaturated intermediate (PLP-bound dehydroalanine). An amino acid sequence comparison indicates that cysteate synthase evolved from an ancestral threonine synthase through gene duplication, and the remodeling of active site loop regions by amino acid insertion and substitutions. The cysteate product can be converted to sulfopyruvate by an aspartate aminotransferase enzyme, establishing a new, convergent pathway for coenzyme M biosynthesis that appears to function in members of the orders Methanosarcinales and Methanomicrobiales. These differences in CoM biosynthesis afford the opportunity to develop methanogen inhibitors that discriminate between the classes of methanogenic archaea.


last changed 2009/12/28 11:45

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