Development of computer programs to automatically find modules and domains of non-robosomal peptide synthetases

Neribosomalno sintetizirani peptidi su sekundarni mikrobni metaboliti, koji predstavljaju veliku i raznovrsnu skupinu biološki aktivnih prirodnih spojeva. Njihov biosintetski put započinje uzastopnom kondenzacijom jednostavnih građevnih jedinica (aminokiselina), te dovodi do izgradnje peptidnih lanaca određenih dužina katalitičkim djelovanjem sintetaza neribosomalnih peptida (NRPS). Znanstvenici su do sada klonirali i sekvencirali vrlo velik broj NRPS-a, no njihove funkcionalnosti i krajnji proizvodi većinom nisu poznati. Sekvenciranje svih tih genskih nakupina ukazuje na mogućnost modeliranja procesa rekombinacije između modularnih sintetaza u uvjetima in silico. To bi pružilo mogućnost predviđanja kemijskih struktura novonastalih supstancija. U ovom je diplomskom radu, za potrebe tog projekta, izrađen novi računalni program, kojem je svrha analiza i detaljno opisivanje nedovoljno opisanih NRPS sustava. Izrađeni računalni program popunjava bazu podataka VCL sekvencijama DNA i proteina modula i domena iz prethodno nedovoljno detaljno opisanih NRPS sustava.Nonribosomal peptides are secondary microbial metabolites which represent large and divers group of biologically active natural products. Their biosynthesis begins with a consecutive condensation of simple building block monomers – aminoacides - (a series of cycles) and leads to construction of peptide chains with defined length by catalytic activity of nonribosomal polypeptide synthetases (NRPS). So far scientists have cloned and sequenced a large number of NRPSs, but their functionalities and final products are mostly unknown. Sequencing of these gene clusters revealed the possibility of modelling the recombination process between modular synthetases in in silico. It would allow the prediction of chemical structure of novel compounds. In this diploma work, a new computer program has been constructed in order to assist the developed project, with a purpose of analysis and annotation of insufficiently described NRPS systems. The constructed computer program add DNA and protein sequences of modules and domains from mentioned NRPS systems into the VCL database