B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction

Nat Commun. 2020 Feb 26;11(1):1058. doi: 10.1038/s41467-020-14867-z.


Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1-7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Our data identify the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Carboxypeptidases / pharmacology*
  • Cardiomegaly / drug therapy*
  • Cardiomegaly / pathology
  • Disease Models, Animal
  • Fibrosis / drug therapy*
  • Fibrosis / pathology
  • Heart Failure / drug therapy
  • Heart Failure / prevention & control
  • Hypertension / drug therapy*
  • Hypertension / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Paenibacillus / enzymology*
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Recombinant Proteins / pharmacology


  • Recombinant Proteins
  • Angiotensin II
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2