New polycyclic tetramate macrolactams with antimycobacterial activity produced by marine-derived Streptomyces sp. KKMA-0239

Satoru Shigeno; Miyu Kadowaki; Kenichiro Nagai; Kanji Hosoda; Takeshi Terahara; Tomoyasu Nishimura; Naoki Hasegawa; Hiroshi Tomoda; Taichi Ohshiro

doi:10.1038/s41429-024-00710-w

New polycyclic tetramate macrolactams with antimycobacterial activity produced by marine-derived Streptomyces sp. KKMA-0239

J Antibiot (Tokyo). 2024 May;77(5):265-271. doi: 10.1038/s41429-024-00710-w. Epub 2024 Mar 26.

Authors

Satoru Shigeno^{1

2}, Miyu Kadowaki^{1

2}, Kenichiro Nagai², Kanji Hosoda^{1

2}, Takeshi Terahara³, Tomoyasu Nishimura⁴, Naoki Hasegawa⁵, Hiroshi Tomoda^{6

7}, Taichi Ohshiro^{8

9}

Affiliations

¹ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
² Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
³ Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo, 108-8477, Japan.
⁴ Keio University Health Center, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
⁵ Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
⁶ 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.
⁷ Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. tomodah@pharm.kitasato-u.ac.jp.
⁸ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. ohshirot@pharm.kitasato-u.ac.jp.
⁹ Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. ohshirot@pharm.kitasato-u.ac.jp.

PMID: 38531967
DOI: 10.1038/s41429-024-00710-w

Abstract

During our screening for anti-mycobacterial agents against Mycobacterium avium complex (MAC), two new polycyclic tetramate macrolactams (PTMs), named hydroxycapsimycin (1) and brokamycin (2), were isolated along with the known PTM, ikarugamycin (3), from the culture broth of marine-derived Streptomyces sp. KKMA-0239. The relative structures of 1 and 2 were elucidated by spectroscopic data analyses, including 1D and 2D NMR. Furthermore, the absolute configuration of 1 was confirmed by a single-crystal X-ray diffraction analysis. Compounds 2 and 3 exhibited moderate antimycobacterial activities against MAC, including clinically isolated drug-resistant M. avium.

Publication types

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

MeSH terms

Anti-Bacterial Agents* / chemistry
Anti-Bacterial Agents* / isolation & purification
Anti-Bacterial Agents* / pharmacology
Antitubercular Agents / chemistry
Antitubercular Agents / isolation & purification
Antitubercular Agents / pharmacology
Crystallography, X-Ray
Lactams*
Lactams, Macrocyclic / chemistry
Lactams, Macrocyclic / isolation & purification
Lactams, Macrocyclic / pharmacology
Magnetic Resonance Spectroscopy
Microbial Sensitivity Tests*
Molecular Structure
Mycobacterium avium Complex / drug effects
Polycyclic Compounds / chemistry
Polycyclic Compounds / isolation & purification
Polycyclic Compounds / pharmacology
Streptomyces* / chemistry
Streptomyces* / metabolism

Substances

Anti-Bacterial Agents
Lactams, Macrocyclic
ikarugamycin
Antitubercular Agents
Polycyclic Compounds
Lactams