Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of renin-angiotensin system and has the beneficial effects on the cardiovascular diseases. We elucidate that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp.B38, has ACE2-like enzymatic activity. In silico analysis revealed the structural similarity between B38-CAP and rhACE2 despite the lack of obvious sequence homology. In vitro recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1-7 with the same potency as rhACE2. Treatment with B38-CAP reduced plasma angiotensin II levels and suppressed angiotensin II-induced hypertension, cardiac hypertrophy and fibrosis in mice. Moreover, continuous infusion of B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Importantly, B38-CAP treatment did not induce overt toxicity of liver and kidney. B38-CAP is an ACE2-like carboxypeptidase, which is functional in vitro and in vivo. B38-CAP could be a novel therapeutics in cardiovascular diseases.These results suggest that the strategy to find molecules of convergent evolution might be effective for drug development, such as ‘generic' protein preparation of functional enzymes.