Amycolatomycins A and B, Cyclic Hexapeptides Isolated from an Amycolatopsis sp. 195334CR.

Gian Primahana,Joachim Wink,Frank Surup,Marc Stadler,Tjandrawati Mozef,Chandra Risdian

doi:10.3390/antibiotics10030261

Gian Primahana, Joachim Wink + Show 4 more

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https://doi.org/10.3390/antibiotics10030261

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Abstract

The rare actinobacterium Amycolatopsis sp. strain 195334CR was found to produce previously undescribed cyclic hexapeptides, which we named amycolatomycin A and B (1 and 2). Their planar structures were determined by high-resolution mass spectrometry as well as extensive 1D and 2D NMR spectroscopy, while the absolute stereochemistry of its amino acids were determined by Marfey’s method. Moreover, 1 and 2 differ by the incorporation of l-Ile and l-allo-Ile, respectively, whose FDVA (Nα-(2,4-Dinitro-5-fluorphenyl)-L-valinamide) derivatives were separated on a C4 column. Their hallmark in common is a unique 2,6-dichloro-tryptophan amino acid unit. Amycolatomycin A (1) exhibited weak activity against Bacillus subtilis DSM 10 (minimum inhibitory concentration (MIC) = 33.4 µg/mL).

Highlights

Microbes continue to serve as a potential storehouse for structurally diverse chemical scaffolds that essentially have been proven for drug discovery [2]
We describe the isolation, structure elucidation, and biological activities of unprecedented cyclic hexapeptides from this strain
A thorough analysis of the crude extract produced by the rare Actinobacterium Amycolatopsis sp strain 195334CR by using high performance liquid chromatography–diode array detector–high-resolution mass spectrometry (HPLC–DAD–HRMS) suggested the presence of novel secondary metabolites

Summary

Introduction

The misuse and overuse of antibiotics have serious consequences of the emergence of antibiotics resistance against currently used antibiotics. This situation led to the urgently needed novel antimicrobial compounds, especially with new modes of action [1]. Microbes continue to serve as a potential storehouse for structurally diverse chemical scaffolds that essentially have been proven for drug discovery [2]. About 65% of currently used antibiotics are derived from Actinobacteria, especially from Streptomyces [3]; making these taxa as the first options for drug discovery screening programs until the end of the 1990s. Due to the massive exploration of Actinobacteria, especially of the genus

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