Abstract

A robust and convenient research strategy integrating state-of-the-art analytical techniques is needed to efficiently discover novel compounds from marine microbial resources. In this study, we identified a series of amino-polyketide derivatives, vitroprocines A-J, from the marine bacterium Vibrio sp. QWI-06 by an integrated approach using imaging mass spectroscopy and molecular networking, as well as conventional bioactivity-guided fractionation and isolation. The structure-activity relationship of vitroprocines against Acinetobacter baumannii is proposed. In addition, feeding experiments with 13C-labeled precursors indicated that a pyridoxal 5′-phosphate-dependent mechanism is involved in the biosynthesis of vitroprocines. Elucidation of amino-polyketide derivatives from a species of marine bacteria for the first time demonstrates the potential of this integrated metabolomics approach to uncover marine bacterial biodiversity.

Highlights

  • The antibacterial activity of these isolated bacteria were screened against nine indicator strains, Gram positive Bacillus cereus, Staphylococcus aureus, Gram negative Klebsiella pneumonia, Salmonella typhimurium, Pseudomonas aeruginosa, Vibrio harveyi, Escherichia coli, and Acinetobacter baumannii, and one fungus strain Candida albicans

  • The 16S rRNA sequence of the strain QWI-06 was close to the type strain Vibrio proteolyticus ATCC 15338 with 99.4% similarity (Supplementary Fig. S2); to our knowledge, this type of bioactivity has not been reported for metabolites obtained from the genus Vibrio

  • The EtOAc extract was further subjected to UPLC-HR-ESIMS/MS for molecular networking analysis and dereplication

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Summary

Introduction

The antibacterial activity of these isolated bacteria were screened against nine indicator strains, Gram positive Bacillus cereus, Staphylococcus aureus, Gram negative Klebsiella pneumonia, Salmonella typhimurium, Pseudomonas aeruginosa, Vibrio harveyi, Escherichia coli, and Acinetobacter baumannii, and one fungus strain Candida albicans. Nineteen of the marine-derived bacteria exhibited significant anti-microbial activities. One strain, QWI-06, showed significant inhibitory activity against A. baumannii, a major pathogen of nosocomial infections in Taiwan (Supplementary Fig. S1). The 16S rRNA sequence of the strain QWI-06 was close to the type strain Vibrio proteolyticus ATCC 15338 with 99.4% similarity (Supplementary Fig. S2); to our knowledge, this type of bioactivity has not been reported for metabolites obtained from the genus Vibrio. We further confirmed that V. proteolyticus ATCC 15338 and its crude extract were inactive against A. baumannii in both antagonistic and anti-bacterial assays. QWI-06 and V. proteolyticus ATCC 15338, using imaging mass spectrometry (IMS) and ultra-performance liquid chromatography– high-resolution electrospray ionization tandem mass spectrometry (UPLC-HR-ESIMS/MS), identified a series of amino-polyketide derivatives, named vitroprocines, from Vibrio sp. A possible biosynthetic pathway, and the structure-activity relationship of the vitroprocines are reported

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