High-Resolution Tandem Mass Spectrometry for Nonribosomal Peptide and Polyketide Analysis

Abstract

The emergence of multidrug resistance in bacteria, fungi, viruses, parasites, and cancer cells drives the constant need to develop novel chemical entities of improved potency and novel mechanisms of action. In this chapter, natural products display a remarkable range of bioactivities and pharmaceutical properties and subsequently accounts for a significant portion of drugs currently available. It introduces high-resolution mass spectrometry and briefly summarizes a number of different mass spectrometry-led strategies to investigate polyketide and nonribosomal peptide biosynthetic precursors. The principle of a tandem mass spectrometry experiment is to obtain structural information on a precursor compound through isolation, fragmentation, and subsequent analysis of the product ions detected. There are a number of tandem mass spectrometry (MS) techniques that can be used for this purpose, the most common of which is collision-activated dissociation (CAD). Different techniques involving mass spectrometry have been applied to assist in the structural characterization of polyketides.