A new tetronomycin analog, broad-spectrum and potent antibiotic against drug-resistant Gram-positive bacteria.

Autor: Kimishima A; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Tsuruoka I; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Tsutsumi H; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Honsho M; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Honma S; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Matsui H; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Sugamata M; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Wasuwanich P; University of Florida College of Medicine, Gainesville, FL 32610, USA., Inahashi Y; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Hanaki H; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan., Asami Y; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.; Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane Minato-ku, 108-8641, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Feb; Vol. 21 (2), pp. e202301834. Date of Electronic Publication: 2024 Feb 01.
DOI: 10.1002/cbdv.202301834
Abstrakt: We discovered a new tetronomycin analog, C-32-OH tetronomycin (2) from the Streptomyces sp. K20-0247 strain, which produces tetronomycin (1). After NMR analysis of 2, we determined the planar structure. Futhermore, the absolute stereochemistry of 2 was deduced based on the biosynthetic pathway of 1 in the K20-0247 strain and a comparison of experimental electronic circular dichroism (ECD) results of 1 with 2. While 2 exihibits potent antibacterial activity aganist Gram-positive baceria including vancomycin-intermediate Staphylococcus aureus (VISA) strains and vancomycin-resistant Enterococci (VRE), the antibacterial activity of 2 shows 16-32-folds weaker than that of 1 suggesting that the C-34 methyl group in 1 is one of the very important functinal group. Moreover, we evaluated the ionophore activity of 1 and 2 and neither compound shows ionophore activity at reasonable concetrations. Our research suggests that 1 and 2 would have different target(s) from an ionophore mechanism in the antibacterial activity and tetronomycins are promising natural products for broad-spectrum antibiotics.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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