In enzymology, a malonate-semialdehyde dehydrogenase (EC 1.2.1.15) is an enzyme that catalyzes the chemical reaction

3-oxopropanoate + NAD(P)+ + H₂O malonate + NAD(P)H + 2 H⁺

The 4 substrates of this enzyme are 3-oxopropanoate, NAD⁺, NADP⁺, and H₂O, whereas its 4 products are malonate, NADH, NADPH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 3-oxopropanoate:NAD(P)+ oxidoreductase. This enzyme participates in beta-alanine metabolism.

• Nakamura K, Bernheim F (June 1961). "Studies on malonic semialdehyde dehydrogenase from Pseudomonas aeruginosa". Biochimica et Biophysica Acta. 50: 147–52. doi:10.1016/0006-3002(61)91071-X. PMID 13727610.