Abyssomicins-A 20-Year Retrospective View.

Hans-Peter Fiedler

doi:10.3390/md19060299

Abstract

Abyssomicins represent a new family of polycyclic macrolactones. The first described compounds of the abyssomicin family were abyssomicin B, C, atrop-C, and D, produced by the marine actinomycete strain Verrucosispora maris AB-18-032, which was isolated from a sediment collected in the Sea of Japan. Among the described abyssomicins, only abyssomicin C and atrop-abyssomicin C show a high antibiotic activity against Gram-positive bacteria, including multi-resistant and vancomycin-resistant strains. The inhibitory activity is caused by a selective inhibition of the enzyme 4-amino-4-deoxychorismate synthase, which catalyzes the transformation of chorismate to para-aminobenzoic acid, an intermediate in the folic acid pathway.

Highlights

An efficient search for new bioactive compounds, such as antibiotics, demands specific requirements: First, there is a need for a massive set of taxonomically characterized and dereplicated microorganisms isolated from terrestrial and/or marine habitats, with a high potency of producing unique secondary metabolites
A representative example of such a source are members of the order Actinomycetales, which are known as potent producers of unique secondary metabolites
The chorismate pathway leads to the biosynthesis of the aromatic amino acids, and to the biosynthesis of para-aminobenzoic acid, an intermediate in the biosynthesis of folic acid

Summary

Introduction

An efficient search for new bioactive compounds, such as antibiotics, demands specific requirements: First, there is a need for a massive set of taxonomically characterized and dereplicated microorganisms isolated from terrestrial and/or marine habitats, with a high potency of producing unique secondary metabolites. The chorismate pathway leads to the biosynthesis of the aromatic amino acids, and to the biosynthesis of para-aminobenzoic acid (pAba), an intermediate in the biosynthesis of folic acid. Mar. Drugs 2021, 19, x FOR PEER REVITEhWe secondary metabolite pattern of the active extract was analyzed by HPLC-diode array, whereby three metabolites were characterized by our HPLC-UV-Vis Database as presumably new compounds, which we named abyssomicins.

The Screening Concept

Taxonomy of the Producing Strain

Increased Abyssomicin Spectrum