In enzymology, a 2-(S)-hydroxypropyl-CoM dehydrogenase (EC 1.1.1.269) is an enzyme that catalyzes the chemical reaction

2-(S)-hydroxypropyl-CoM + NAD⁺ ${\displaystyle \rightleftharpoons }$ 2-oxopropyl-CoM + NADH + H⁺

Thus, the two substrates of this enzyme are 2-(S)-hydroxypropyl-CoM and NAD⁺, whereas its 3 products are 2-oxopropyl-CoM, NADH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 2-[2-(S)-hydroxypropylthio]ethanesulfonate:NAD⁺ oxidoreductase. This enzyme is also called 2-(2-(S)-hydroxypropylthio)ethanesulfonate dehydrogenase.

• Allen JR, Clark DD, Krum JG, Ensign SA (1999). "A role for coenzyme M (2-mercaptoethanesulfonic acid) in a bacterial pathway of aliphatic epoxide carboxylation". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8432–7. Bibcode:1999PNAS...96.8432A. doi:10.1073/pnas.96.15.8432. PMC 17533. PMID 10411892.