PT  - JOURNAL ARTICLE
AU  - Jacob Gubbens
AU  - Changsheng Wu
AU  - Hua Zhu
AU  - Dmitri V. Filippov
AU  - Bogdan I. Florea
AU  - Sébastien Rigali
AU  - Herman S. Overkleeft
AU  - Gilles P. van Wezel
TI  - Qinichelins, novel catecholate-hydroxamate siderophores synthesized via a multiplexed convergent biosynthesis pathway
AID  - 10.1101/163170
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 163170
4099  - http://biorxiv.org/content/early/2017/07/13/163170.short
4100  - http://biorxiv.org/content/early/2017/07/13/163170.full
AB  - 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 (BGC; named qch) most likely responsible for qinichelin biosynthesis. The structure of the molecules was elucidated by bioinformatics, mass spectrometry and NMR. Synthesis of the qinichelins requires the interplay between four gene clusters, for its synthesis and for precursor supply. This biosynthetic complexity provides new insights into the challenges scientists face when applying synthetic biology approaches for natural product discovery.Pride repository reviewer account details:URL: https://www.ebi.ac.uk/pride/archive/loginProject accession: PXD006577Username: reviewer35793@ebi.ac.ukPassword: 3H0iM1FK