engleski

Bioinformatic tools for mining large DNAS data sets

The program package ClustScan is designed for rapid, semi-automatic, annotation of DNA sequences encoding modular biosynthetic enzymes including polyketide synthases (PKS), non-ribosomal peptide synthetases (NRPS) and hybrid (PKS/NRPS) enzymes. Potential protein coding regions and protein domains are identified by programs running on a server and the results are presented to the user in a graphical interface with a Java client program. The user can edit the results and assemble biosynthetic clusters. The versatility of this program package has been demonstrated by annotating biochemical pathways in microbial, invertebrate animal and metagenomic datasets. The novelty of ClustScan over existing computer programs is the automatic prediction of substrate activity and specificity, as well as steriochemical outcomes of biosynthetic pathways, allowing linear and cyclic chemical structures to be deduced in silico. The open architecture of ClustScan allows easy integration with other programs, facilitating further analyses of results, which would be of use to a broad range of researchers in the chemical and biological sciences. There are two main criteria for the usefulness of ClustScan. The accuracy of prediction and the speed and convenience of annotating large DNA data sets. The accuracy of prediction will be demonstrated using the well-known gene cluster encoding the erythromycin biosynthetic pathway. The speed and convenience of annotating large DNA data sets will also be demonstrated using genomic and metagenomic data sets. The modular biosynthetic clusters in an actinomycete genome sequence can be annotated by a single person in about 3 hours. The ClustScan program package will be demonstrated online during the meeting on reguest. To download ClustScan and access services, one should go to the Web site http://reg.bioserv.pbf.hr/. STARCEVIC, Antonio, ZUCKO, Jurica, SIMUNKOVIC, Jurica, LONG, F. Paul, CULLUM, John, HRANUELI, Daslav. ClustScan: Semi-automatic annotation of modular gene clusters and prediction of chemical structures. Nucleic Acids Res., 2008 (submitted). STARCEVIC, Antonio, AKTHAR, Shamima, DUNLAP, C. Walter, SHICK, J. Malcolm, HRANUELI, Daslav, CULLUM, John, LONG, F. Paul. Enzymes of the shikimic acid pathway encoded in the genome of a basal metazoan, Nematostella vectensis, have microbial origins. Proc. Natl. Acad. Sci. U.S.A., 105, 2533-2537, 2008. ZUCKO, Jurica, SKUNCA, Nives, CURK, Tomaz, ZUPAN, Blaz, LONG, F. Paul, CULLUM, John, KESSIN, Richard, HRANUELI, Daslav. Polyketide synthase genes and the natural products potential of Dictyostelium discoideum. Bioinformatics, 23, 2543– 2549, 2007.

polyketides; non-ribosomal peptides; Actinobacteria; metagenomes; genomes; gene clusters

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