An Enzyme Containing the Conserved Domain of Unknown Function DUF62 Acts as a Stereoselective (Rs ,Sc )-S-Adenosylmethionine Hydrolase.

Homochirality is a signature of biological systems. The essential and ubiquitous cofactor S-adenosyl-l-methionine (SAM) is synthesized in cells from adenosine triphosphate and l-methionine to yield exclusively the (S,S)-SAM diastereomer. (S,S)-SAM plays a crucial role as the primary methyl donor in transmethylation reactions important to the development and homeostasis of all organisms from bacteria to humans. However, (S,S)-SAM slowly racemizes at the sulfonium center to yield the inactive (R,S)-SAM, which can inhibit methyltransferases. Control of SAM homochirality has been shown to involve homocysteine S-methyltransferases in plants, insects, worms, yeast, and in ∼18 % of bacteria. Herein, we show that a recombinant protein containing a domain of unknown function (DUF62) from the actinomycete bacterium Salinispora tropica functions as a stereoselective (R,S)-SAM hydrolase (adenosine-forming). DUF62 proteins are encoded in the genomes of 21 % of bacteria and 42 % of archaea and potentially represent a novel mechanism to remediate SAM damage.