Binding Mode-Based Physicochemical Screening Method Using d‑Ala‑d‑Ala Silica Gel and Chemical Modification Approach to Facilitate Discovery of New Macrolactams, Banglactams A and B, from Nonomuraea bangladeshensis K18–0086

• Published in: ACS omega 2024-04, Vol.9 (15), p.17415-17422
• Main Authors: Kimishima, Aoi, Suzuki, Yuki, Kosaka, Shohei, Honsho, Masako, Honma, Sota, Tsutsumi, Hayama, Inahashi, Yuki, Watanabe, Yoshihiro, Nakashima, Takuji, Asami, Yukihiro, Iwatsuki, Masato
• Format: Article
• Language: English
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.4c00145

Utilizing a binding mode-based physicochemical screening method using d-Ala-d-Ala silica gel, two new macrolactams, named banglactams A (1) and B (2), were discovered from the culture broth of Nonomuraea bangladeshensis K18–0086. In the course of our investigation, we found that d-Ala-d-Ala silica gel precisely differentiated the chemical structures of banglactams and separated them. However, we were not able to obtain enough of 1 to elucidate the structure due to its instability and insolubility. To overcome this challenge, we chemically modified 1 to improve solubility, enabling us to obtain a sufficient material supply for the indirect determination of the structure. Antibacterial activity evaluation of banglactams revealed that 1 binding to d-Ala-d-Ala silica gel exhibited antibacterial activity against Staphylococcus aureus; however, this was not the case with 2. This research indicates the utility of our original binding mode-based PC screening method, and the combination strategy of PC and chemical modifications led us to discover novel antibacterial compounds.