Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry to reveal the substrate specificity of the peptidyl-cysteine decarboxylase EpiD

The microbial flavoenzyme EpiD catalyzes the oxidative decarboxylation of peptidyl‐cysteines to peptidyl‐aminoenethiols. These unusual C‐terminally modified peptides are intermediates in the biosynthesis of the tetracyclic peptide antibiotic epidermin, which belongs to the lantibiotics family. The peptide SFNSYCC represents the C‐terminal partial sequence of the natural precursor peptide EpiA. EpiA is posttranslationally modified to form finally the lantibiotic epidermin. The substrate specificity of EpiD was investigated using high‐resolution mass spectrometry and the heptapeptide library SFNSXCC. The enzymatic conversion of particular peptides can be observed by a mass loss of m/z 46. In contrast to the previously used triple quadrupole instrument, electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI‐FTICR‐MS) was able to resolve and detect all precursor and converted peptides with identical nominal masses in a single measurement, avoiding the necessity to investigate single peptides. Furthermore, a new substrate SFNSCCC of the enzyme EpiD was detected within the reaction mixture. Copyright © 2002 John Wiley & Sons, Ltd.