Predviđanje funkcija domena poliketidnih sintetaza pomoću skrivenih Markovljevih modela

master's thesis

• Title (english): Function prediction of polyketide synthase domains using hidden Markov models
• Author: Jurica Žučko
• Mentor: Daslav Hranueli (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Section for Bioinformatics); Zagreb
• Defense date and country: 2005-06-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Poliketidi su jedna od najčešće upotrebljavanih vrsta spojeva za dobivanje novih, biološki aktivnih supstancija. Razlog tome je način njihove biosinteze, koja se odvija u stupnjevima, pri čemu se u svakom stupnju poliketidni lanac produži za dva ugljikova atoma. Za dobivanje novih spojeva najčešće se upotrebljava postupak kombinatorne biosinteze, dodavanjem, uklanjanjem ili zamjenom domena ili modula poliketidnih sintetaza. Tim postupkom su dobiveni novi poliketidni spojevi, ali je njihov prinos u pravilu nizak. Kako taj problem nije razriješen, razvijen je novi postupak za dobivanje novih poliketida – mjesno-specifična mutageneza. Zamjenom pojedinih aminokiselina AT domena uspjela se promijeniti njihova specifičnost za supstrat. Matematički model, testiran u ovom radu, traži unutar višestrukog poravnanja domena stupce koji bi mogli imati važnu ulogu u određivanju funkcije domene. Zamjenom aminokiselina na tim pozicijama mogla bi se promijeniti funkcija domene.

Abstract (english)

The polyketide natural products are a group of chemical compounds most frequently used to obtain new biologically active substances. The reason for that is their stepwise way of biosynthesis, where in each step the polyketide chain grows by two carbon atoms. Combinatorial biosynthesis is mostly used for obtaining new polyketides by adding, deleting or swapping domains or modules of the polyketide synthases. Numerous new compounds were synthesised using combinatorial biosynthesis, but the product titre was too low for commercial production. Since this problem has not been solved yet, a new approach using site-specific mutagenesis was developed. Until now the change of AT domain substrate specificity was achieved by substituting a few amino acids. The mathematical model tested in this work searches within multiple alignment for columns that might play an important role in determining the function of the domain. Changing the amino acids on those positions should alter the function of the domain.

• Keywords: analiza sekvenci; evolucija aminokiselina unutar domena; predviđanje funkcija domena; skriveni Markovljev model
• Keywords (english): sequence analysis; amino acid evolution within domain; function prediction; hidden Markov model
• Language: croatian
• URN:NBN: urn:nbn:hr:159:054195
• Study programme: Title: Biotechnology; specializations in: Biochemical Engineering; Course: Biochemical Engineering; Study programme type: university; Study level: graduate; Academic / professional title: diplomirani inženjer biotehnologije; smjer biokemijsko inženjerstvo (diplomirani inženjer biotehnologije; smjer biokemijsko inženjerstvo)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-09-13 09:27:41