An Enzyme Containing the Conserved Domain of Unknown Function DUF62 Acts as a Stereoselective ( R s ,S c )‐ 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.