Nonribosomal Peptide Analog Identification with Tandem Mass Spectrometry

Nonribosomal Peptide;Analog;Mass Spectrometry;Computer Science

Shiwei, Li

University of Waterloo

关键词: Nonribosomal Peptide;    Analog;    Mass Spectrometry;    Computer Science;   

Others  :  https://uwspace.uwaterloo.ca/bitstream/10012/8584/1/Li_Shiwei.pdf

瑞士|英语

来源: UWSPACE Waterloo Institutional Repository

【 摘 要 】

Nonribosomal peptides (NRP) are a class of peptide secondarymetabolites, usually produced by microorganisms like bacteria and fungi. NRPantibiotics, cytostatics, and immunosuppressants are in commercial use. Inpharmacological studies, novel NRPs are often promising substances for newdrug development. To discover novel NRPs with limited resources frommicrobial fermentations, a significant process is to identify known NRPs andtheir analogs in an early stage and exclude them from further investigation.This so-called ;;dereplication” step ensures less resource wasted in thesubsequent experiments. Tandem mass spectrometry has been routinely usedfor NRP dereplication. Other researchers have developed software to identifyknown NRPs with a database. However, only a rather small part of NRPs arediscovered by now and identifying analog of these NRPs is still occupyingmuch resources and hindering the throughput of novel NRP discovery.In this thesis, we review the nature of nonribosomal peptides andinvestigate the challenges in computationally solving the analog findingproblem. After that, a program called NRP Analog Finder is introduced as anautomated method to identify NRPs and their analogs with tandem massspectrometry. It is designed to identify mixtures of NRP compounds fromLC-MS/MS of complex extract; find structural analogs that differ from anidentified known NRP compound with at most two monomers; localize themodified residues; and determine how much mass is changed at eachmodification site. NRP analog finder is tested to be an effective tool for massspectrometry based NRP analog identification.