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Krisynomycins, Imipenem Potentiators against Methicillin-Resistant Staphylococcus aureus, Produced by Streptomyces canus

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journal contribution
posted on 12.09.2020, 12:29 by Mercedes Pérez-Bonilla, Daniel Oves-Costales, Ignacio González, Mercedes de la Cruz, Jesús Martín, Francisca Vicente, Olga Genilloud, Fernando Reyes
A reinvestigation of the acetone extract of the strain CA-091830 of Streptomyces canus, producer of the imipenem potentiator krisynomycin, resulted in the isolation of two additional analogues, krisynomycins B (1) and C (2), with different chlorination patterns. Genome sequencing of the strain followed by detailed bioinformatics analysis led to the identification of the corresponding biosynthetic gene cluster (BGC) of this cyclic nonribosomal peptide family. The planar structure of the new molecules was determined using HRMS, ESI-qTOF-MS/MS, and 1D and 2D NMR data. Their absolute configuration was proposed using a combination of Marfey’s and bioinformatic BGC analyses. The krisynomycins displayed weak to negligible antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA), which was significantly enhanced when tested in combination with sublethal concentrations of imipenem. The halogenation pattern plays a key role in the antimicrobial activity and imipenem-potentiating effects of the compounds, with molecules having a higher number of chlorine atoms potentiating the effect of imipenem at lower doses.

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