JBIR-155, a Specific Class D β-Lactamase Inhibitor of Microbial Origin

Takehiro Nishimura; Teppei Kawahara; Noritaka Kagaya; Yusuke Ogura; Hirosato Takikawa; Hikaru Suenaga; Masaatsu Adachi; Takatsugu Hirokawa; Takayuki Doi; Kazuo Shin-Ya

doi:10.1021/acs.orglett.1c01352

JBIR-155, a Specific Class D β-Lactamase Inhibitor of Microbial Origin

Org Lett. 2021 Jun 4;23(11):4415-4419. doi: 10.1021/acs.orglett.1c01352. Epub 2021 May 24.

Authors

Takehiro Nishimura¹, Teppei Kawahara², Noritaka Kagaya¹, Yusuke Ogura³, Hirosato Takikawa³, Hikaru Suenaga⁴, Masaatsu Adachi⁵, Takatsugu Hirokawa^{4

6

7}, Takayuki Doi⁵, Kazuo Shin-Ya^{1

4

8}

Affiliations

¹ Technology Research Association for Next Generation Natural Products Chemistry, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
² Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064 Japan.
³ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
⁴ National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
⁵ Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
⁶ Division of Biomedical Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
⁷ Transborder Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
⁸ Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

PMID: 34029112
DOI: 10.1021/acs.orglett.1c01352

Abstract

We discovered JBIR-155 as a novel specific class D β-lactamase inhibitor from Streptomyces polymachus SoB100815Hv02. JBIR-155 consists of a 6-oxabicyclo[3.2.0]heptan-7-one skeleton and a long unsaturated alkyl chain moiety of which absolute configuration was determined by spectroscopic data, modified Mosher's method, and analyses of the relative configuration of chemically modified derivative. JBIR-155 specifically exhibited inhibitory activity against the class D β-lactamase, with an IC₅₀ value of 0.36 μM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Streptomyces / chemistry*
beta-Lactamase Inhibitors / chemistry*
beta-Lactamase Inhibitors / pharmacology*

Substances

Anti-Bacterial Agents
beta-Lactamase Inhibitors

Supplementary concepts

Streptomyces polymachus