Identification and activation of novel biosynthetic gene clusters by genome mining in the kirromycin producer Streptomyces collinus Tü 365

Abstract

Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein biosynthesis interacting with elongation factor EF-Tu. Genome Mining revealed 32 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of Streptomyces collinus Tü 365, indicating an enormous biosynthetic potential of this strain. The structural diversity of secondary metabolisms predicted for S. collinus Tü 365 includes PKS, NRPS, PKS-NRPS hybrids, a lanthipeptide, terpenes and siderophores. While some of these gene clusters were found to contain genes related to known secondary metabolites, which also could be detected in HPLC-MS analyses, most of the uncharacterized gene clusters are not expressed under standard laboratory conditions. With this study we aimed to characterize the genome information of S. collinus Tü 365 to make use of gene clusters, which previously have not been described for this strain. We were able to connect the gene clusters of a lanthipeptide, a carotenoid, five terpenoid compounds, an ectoine, a siderophore and a spore pigment-associated gene cluster to their respective biosynthesis products.

The evolution of genome mining in microbes – a review

“…While no signicant antibacterial or antiviral activity was detected for streptocollin, a moderate inhibitory activity towards protein-tyrosine-phosphatase 1B, a potential target to treat type 2 diabetes or obesity, was observed. 113 Similar to NRPs, the combination of genome mining with computational mass spectrometry approaches provides valuable tools for the identication of novel compounds. 103,116 One of the rst peptides identied with this method was the type III lanthipeptide informatipeptin produced by Streptomyces viridochromogenes DSM 40736.…”

Streptocollin, a Type IV Lanthipeptide Produced by Streptomyces collinus Tü 365

“…Mining the genome data of S. collinus Tü 365 with the software antiSMASH [16] revealed 32 gene clusters for secondary metabolites. [15] Three, including the kirromycin cluster,a re duplicated on the long terminal inverted repeats of the chromosome. One of these three encodes ap utative lanthipeptide biosynthesis pathway.…”

“…[13] The genome of S. collinus Tü 365 was fully sequenced and annotated: 8.27 Mb encoding 7116 proteins. [14] Ag enome mininga pproach [15] led to the identification of an ew representative of class IV lanthipeptides in S. collinus Tü 365. Here we report the identification, cloning, and analysis of this lanthipeptide,w hich we name streptocollin.…”

Acyltransferases as Tools for Polyketide Synthase Engineering

“…Therefore, bioactive product discovery methods, which are based on traditional, bioactivity-guided screening and compound isolation are still relevant. There is even a renewed interest in this approach as a strategy for the identification of new drugs [ 15 , 16 , 17 , 18 , 19 ]. In particular, the developments in molecular biology, synthetic biology, sequencing technology, chemistry, and bioinformatics provide new opportunities for the classic screening programs and compound recovery from the natural environment.…”