Kimidinomycin, a new antibiotic against Mycobacterium avium complex, produced by Streptomyces sp. KKTA-0263

Ayumi Hikima; Shumpei Asamizu; Hiroyasu Onaka; Huiping Zhang; Hiroshi Tomoda; Nobuhiro Koyama

doi:10.1038/s41429-021-00494-3

Kimidinomycin, a new antibiotic against Mycobacterium avium complex, produced by Streptomyces sp. KKTA-0263

J Antibiot (Tokyo). 2022 Feb;75(2):72-76. doi: 10.1038/s41429-021-00494-3. Epub 2021 Dec 23.

Authors

Ayumi Hikima¹, Shumpei Asamizu², Hiroyasu Onaka², Huiping Zhang³, Hiroshi Tomoda^{4

5}, Nobuhiro Koyama^{6

7}

Affiliations

¹ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
² Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
³ RIKEN SPring-8 Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
⁴ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. tomodah@pharm.kitasato-u.ac.jp.
⁵ Drug Discovery Laboratory, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. tomodah@pharm.kitasato-u.ac.jp.
⁶ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. koyaman@pharm.kitasato-u.ac.jp.
⁷ Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. koyaman@pharm.kitasato-u.ac.jp.

PMID: 34949834
DOI: 10.1038/s41429-021-00494-3

Abstract

During our screening for antibiotics against Mycobacterium avium complex (MAC) with a mass spectrometry network-based indexing approach, a new compound named kimidinomycin was isolated from the culture broth of Streptomyces sp. KKTA-0263 by solvent extraction, HP20 column chromatography, and preparative HPLC. From the structural elucidation, the compound possesses a 38-membered macrolide structure with an N-methylguanidyl group at the terminal side chain. The compound exhibited antimycobacterial activity against M. avium, M. intracellulare, M. smegmatis, and M. bovis BCG with respective MIC values of 12.5, 0.78, 12.5, and 25.0 µg ml^-1.

Publication types

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

MeSH terms

Animals
Antibiotics, Antitubercular* / biosynthesis
Antibiotics, Antitubercular* / pharmacology
Antibiotics, Antitubercular* / toxicity
CHO Cells
Chromatography, High Pressure Liquid
Cricetinae
Cricetulus
Fermentation
HeLa Cells
Humans
Macrolides / chemistry
Microbial Sensitivity Tests
Mycobacterium avium Complex* / drug effects
Mycobacterium avium-intracellulare Infection
Mycobacterium bovis / drug effects
Mycobacterium smegmatis / drug effects
Streptomyces* / metabolism

Substances

Antibiotics, Antitubercular
Macrolides
kimidinomycin