Natural products such as polyketides are a fertile target for drug discovery. Methodologies relating to discovery, metabolism, synthesis and biosynthesis of polyketides have evolved considerably since they were first studied in the early 20th century. The antibiotic erythromycin, produced by the Streptomyces erythreus bacteria, was the first of the macrolide natural products to be discovered in 1952. The biosynthesis of erythromycin is catalysed by a large multifunctional enzyme, which constructs the polyketide intermediate that is acted upon by tailoring enzymes to produce the final construct. It is during this process that molecular diversity is generated, and commercial samples of erythromycin tend to be mixtures of co-metabolites. To fully identify these compounds, a full fragmentation scheme of the main component (erythromycin A) is required, which is absent from the literature. In this study, accurate-mass sequential mass spectrometry is used to propose a fragmentation scheme which is then used to assign structures to eight co-metabolites including the identification of a previously unpublished form of erythromycin. This clearly demonstrates the successful application of the methodology.
Jiang et al. (Wed,) studied this question.