Intertwined Precursor Supply during Biosynthesis of the Catecholate–Hydroxamate Siderophores Qinichelins in Streptomyces sp. MBT76

Abstract

The explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites, representing a huge unexploited pool of chemical diversity. Here, we describe the discovery of a novel group of catecholate–hydroxamate siderophores termed qinichelins (2–5) from Streptomyces sp. MBT76. Correlation between the metabolite levels and the protein expression profiles identified the biosynthetic gene cluster (named qch) most likely responsible for qinichelin biosynthesis. The structure of the molecules was elucidated by bioinformatics, mass spectrometry, and NMR. The genome of Streptomyces sp. MBT76 contains three gene clusters for the production of catecholate–peptide siderophores, including a separate cluster for the production of a shared catecholate precursor. In addition, an operon in the qch cluster was identified for the production of the ornithine precursor for qinichelins, independent of primary metabolism. This biosynthetic complexity provides new insights into the challenges scientists face when applying synthetic biology approaches for natural product discovery.

Polyphasic classification of the gifted natural product producer Streptomyces roseifaciens sp. nov.

“…Based on its genome sequence, MBT76 was positioned within the genus Streptomyces [2]. Strain MBT76 T is a gifted strain that produces various novel antibiotics and siderophores [2][3][4][5], its genome contains at least 44 biosynthetic gene clusters (BGCs) for specialized metabolites as identified by antiSMASH [6]. ]The importance of validly naming novel industrially important streptomycetes is often overlooked despite improvements in the classification of the genus Streptomyces [7][8][9] and adherence to the rules embodied in the International Code of Nomenclature of Prokaryotes [10].…”

Cloning and Overexpression of the Toy Cluster for Titer Improvement of Toyocamycin in Streptomyces diastatochromogenes

“…Preliminary results indicate an explosive increase in TM production in this strain (data not shown). We are now planning to further investigate the strain, perform genome engineering ( Huang et al, 2015 ; Li et al, 2017 ) and a precursor feeding strategy ( Zabala et al, 2013 ; Gubbens et al, 2017 ; Zheng et al, 2019 ) to further improve TM production.…”

Mining for Microbial Gems: Integrating Proteomics in the Postgenomic Natural Product Discovery Pipeline

“…For these methods to be successful, a prerequisite is to achieve significant fluctuation in the metabolome. This was achieved via the use of elicitors or changing growth conditions or via altered expression of mutation of regulatory genes via directed or random mutagenesis …”