Nonribosomal Peptide Analog Identification with Tandem Mass Spectrometry
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Date
2014-07-29
Authors
Shiwei, Li
Journal Title
Journal ISSN
Volume Title
Publisher
University of Waterloo
Abstract
Nonribosomal peptides (NRP) are a class of peptide secondary
metabolites, usually produced by microorganisms like bacteria and fungi. NRP
antibiotics, cytostatics, and immunosuppressants are in commercial use. In
pharmacological studies, novel NRPs are often promising substances for new
drug development. To discover novel NRPs with limited resources from
microbial fermentations, a significant process is to identify known NRPs and
their analogs in an early stage and exclude them from further investigation.
This so-called “dereplication” step ensures less resource wasted in the
subsequent experiments. Tandem mass spectrometry has been routinely used
for NRP dereplication. Other researchers have developed software to identify
known NRPs with a database. However, only a rather small part of NRPs are
discovered by now and identifying analog of these NRPs is still occupying
much resources and hindering the throughput of novel NRP discovery.
In this thesis, we review the nature of nonribosomal peptides and
investigate the challenges in computationally solving the analog finding
problem. After that, a program called NRP Analog Finder is introduced as an
automated method to identify NRPs and their analogs with tandem mass
spectrometry. It is designed to identify mixtures of NRP compounds from
LC-MS/MS of complex extract; find structural analogs that differ from an
identified known NRP compound with at most two monomers; localize the
modified residues; and determine how much mass is changed at each
modification site. NRP analog finder is tested to be an effective tool for mass
spectrometry based NRP analog identification.
Description
Keywords
Nonribosomal Peptide, Analog, Mass Spectrometry