Genome Mining and Metabolomics Unveil Pseudonochelin: A Siderophore Containing 5-Aminosalicylate from a Marine-Derived Pseudonocardia sp. Bacterium

Abstract

Pseudonochelin (1), a siderophore from a marine-derived Pseudonocardia sp. bacterium, was discovered using genome mining and metabolomics technologies. A 5-aminosalicylic acid (5-ASA) unit, not previously found in siderophore natural products, was identified in 1. Annotation of a putative psn biosynthetic gene cluster combined with bioinformatics and isotopic enrichment studies enabled us to propose the biosynthesis of 1. Moreover, 1 was found to display in vitro and in vivo antibacterial activity in an iron-dependent fashion.

Figure 1.

(a) PCA scores plot showing that WMMC193 has a highly variant metabolome versus other library strains. (b) PCA loadings plot shows unique molecular features for WMMC193. (c) The structure of 1.

Figure 2.

Regression analysis of experimental ¹³C NMR data for 1 versus computationally calculated ¹³C NMR chemical shifts for 1a/1b. (a) Two possible structures of 1. (b) Plots (linear fitting) of the calculated versus the experimental ¹³C NMR chemical shifts for C-29–C-34.

Figure 3.

Putative pseudonochelin biosynthetic gene cluster and proposed pathway for pseudonochelin biosynthesis. (a) Organization of the psn cluster. (b) Proposed biosynthetic roles of PsnN and PsnP. (c) Proposed biosynthetic pathway of pseudonochelin.