The structure of CgnJ, a domain of unknown function protein from the crocagin gene cluster

Abstract

Natural products often contain interesting new chemical entities that are introduced into the structure of a compound by the enzymatic machinery of the producing organism. The recently described crocagins are novel polycyclic peptides which belong to the class of ribosomally synthesized and post‐translationally modified peptide natural products. They have been shown to bind to the conserved prokaryotic carbon‐storage regulator A in vitro. In efforts to understand crocagin biosynthesis, the putative biosynthetic genes were expressed and purified. Here, the first crystal structure of a protein from the crocagin‐biosynthetic gene cluster, CgnJ, a domain of unknown function protein, is reported. Possible functions of this protein were explored by structural and sequence homology analyses. Even though the sequence homology to proteins in the Protein Data Bank is low, the protein shows significant structural homology to a protein with known function within the competency system of Bacillus subtilis, ComJ, leading to the hypothesis of a similar role of the protein within the producing organism.

Genome-Guided Discovery of the First Myxobacterial Biarylitide Myxarylin Reveals Distinct C–N Biaryl Crosslinking in RiPP Biosynthesis

“…Although several bioinformatics tools have recently been developed [8][9][10][11][12][13] or successively updated [14] to allow for the automated detection of certain classes of RiPPs, there is likely still an abundance of yet-undiscovered RiPPs that may have been overlooked in the past [15]. Since the fulvocins [16,17], xanthacin [18], the crocagins [19,20] and the cittilins [21][22][23] are the only myxobacterial RiPPs that have been identified and partly characterized up to date, myxobacteria likely provide an underexploited reservoir for the discovery of new RiPPs. Among these few known myxobacterial RiPPs, the biosynthesis of the cittilins is remarkable, since it only requires a 27-amino-acid precursor peptide which is enzymatically modified by the cytochrome-P450-dependent enzyme CitB to form a bridged tetrapeptide containing a biaryl and an aryl-oxy-aryl link [21].…”

Genome-guided Discovery of the First Myxobacterial Biarylitide Myxarylin Reveals Distinct C–N Biaryl Crosslinking in RiPP Biosynthesis

“…[7] Although several bioinformatics tools have recently been developed [8][9][10][11][12][13] or successively updated [14] to allow automated detection of certain classes of RiPPs, there is likely still an abundance of yet undiscovered RiPPs that may have been overlooked in the past. [15] Since the fulvocins [16,17], xanthacin [18], the crocagins [19,20] and the cittilins [21][22][23] are the only myxobacterial RiPPs that have been identified and partly characterized up to date, myxobacteria likely provide an underexploited reservoir for the discovery of new RiPPs. Among these few known myxobacterial RiPPs, the biosynthesis of the cittilins is remarkable, since it only requires a 27 amino acid precursor peptide which is enzymatically modified by the cytochrome P450 dependent enzyme CitB to form a bridged tetrapeptide containing a biaryl and an aryl-oxy-aryl link.…”