Author
Listed:
- Takafumi Minato
(Akita University Graduate School of Medicine)
- Satoru Nirasawa
(Japan International Research Center for Agricultural Sciences)
- Teruki Sato
(Akita University Graduate School of Medicine
Akita University Graduate School of Medicine)
- Tomokazu Yamaguchi
(Akita University Graduate School of Medicine)
- Midori Hoshizaki
(National Institute of Biomedical Innovation, Health and Nutrition)
- Tadakatsu Inagaki
(Research Institute National Cerebral and Cardiovascular Center)
- Kazuhiko Nakahara
(Japan International Research Center for Agricultural Sciences)
- Tadashi Yoshihashi
(Japan International Research Center for Agricultural Sciences)
- Ryo Ozawa
(Akita University Graduate School of Medicine)
- Saki Yokota
(Akita University)
- Miyuki Natsui
(Akita University Graduate School of Medicine)
- Souichi Koyota
(Akita University)
- Taku Yoshiya
(Peptide Institute, Inc.)
- Kumiko Yoshizawa-Kumagaye
(Peptide Institute, Inc.)
- Satoru Motoyama
(Akita University Graduate School of Medicine)
- Takeshi Gotoh
(Akita University)
- Yoshikazu Nakaoka
(Research Institute National Cerebral and Cardiovascular Center)
- Josef M. Penninger
(IMBA -Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Campus Vienna BioCenter
University of British Columbia)
- Hiroyuki Watanabe
(Akita University Graduate School of Medicine)
- Yumiko Imai
(National Institute of Biomedical Innovation, Health and Nutrition)
- Saori Takahashi
(Akita Research Institute of Food and Brewing)
- Keiji Kuba
(Akita University Graduate School of Medicine)
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.
Suggested Citation
Takafumi Minato & Satoru Nirasawa & Teruki Sato & Tomokazu Yamaguchi & Midori Hoshizaki & Tadakatsu Inagaki & Kazuhiko Nakahara & Tadashi Yoshihashi & Ryo Ozawa & Saki Yokota & Miyuki Natsui & Souichi, 2020.
"B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction,"
Nature Communications, Nature, vol. 11(1), pages 1-12, December.
Handle:
RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14867-z
DOI: 10.1038/s41467-020-14867-z
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