Abstract

A new thiopeptide (micrococcin P3, 1) and a known one (micrococcin P1, 2) were isolated from the culture broth of a marine-derived strain of Bacillus stratosphericus. The structures of both compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR analysis, high resolution mass spectrometry (HRMS), and tandem mass spectrometry. Both compounds exhibited potent antibacterial activities against Gram-positive strains with minimum inhibitory concentration (MIC) values of 0.05−0.8 μg/mL and did not show cytotoxicity in the MTT assay up to a concentration of 10 μM. This study adds a new promising member, micrococcin P3, to the family of thiopeptide antibiotics, which shows potential for the development of new antibiotics targeting Gram-positive bacteria.

Highlights

  • Natural product-derived antibiotics have provided humankind with an effective weapon to fend off bacterial infections and diseases since their discovery in 1929

  • During our ongoing program toward the discovery of new antibiotics, 32 marine-derived bacterial strains were screened by minimum inhibitory concentration (MIC) bioassays and surveyed by LC-MS screening

  • Micrococcin P3 (1), a white amorphous powder, was determined to have a molecular formula of C48 H49 N13 O9 S6 by high resolution electrospray ionization mass spectrometry (ESIMS) data (m/z 1144.2185, calc. for [M + H]+ 1144.2179)

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Summary

Introduction

Natural product-derived antibiotics have provided humankind with an effective weapon to fend off bacterial infections and diseases since their discovery in 1929. Increasing resistance to antibiotics reduces the treatment options available for patients and imposes significant economic burdens on patients due to prolonged stays in hospitals. Medical procedures, such as major surgery and cancer chemotherapy, would become very risky without effective antibiotics to prevent and treat infections. Antibiotic resistance is a major global healthcare concern In this context, it is more critical than ever to discover new and effective antibiotics to overcome this worldwide public health crisis. During our ongoing program toward the discovery of new antibiotics, 32 marine-derived bacterial strains were screened by MIC (minimum inhibitory concentration) bioassays and surveyed by LC-MS (liquid chromatography-mass spectrometry) screening. The isolation, structure elucidation, and antibacterial activity of micrococcins P1 and P3 are described

Structural Elucidation of the Compounds
Antibacterial
Solubility Issues with Thiopeptides
General Experimental Procedures
Strain and Cultivation
Extraction and Isolation of Compounds
Antibacterial Activity Assay
Cell Viability Assay
Conclusions
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