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

Abstract

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.

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“…Increasing data demonstrate that angiotension converting enzyme (ACE)2, as a receptor for SARS-CoV-2, exerts a signi cant role in the pathogenesis of COVID-19 patients [22][23][24]. Recently, a report found that ACE2 was also expressed in cardiocytes [25]. Hence, these evidences don't exclude that SARS-CoV-2 evokes myocardial injury partially through directly damaging myocardial cells.…”

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“…The newly identified bacterial derived B38-CAP enzyme has been found similar to that of human ACE2-like enzyme. Its protective effects are suppressing hypertension and cardiac dysfunction and subsequent lung injury [ 125 ]. Use of this bacterial strain with B38-CAP enzyme or identification of other bacterial strains with similar properties might play a beneficial role in controlling/decreasing the severity and pathogenesis of COVID-19 while working as an alternative ACE2 receptor for SARS-CoV2 instead of human tissue.…”