Dereplication and de novo sequencing of nonribosomal peptides

Abstract
Multistage mass spectrometry and algorithms for spectral alignment and dereplication allow sequencing of nonribosomal peptides, pharmacologically important compounds that are not encoded in the genome but built by nonribosomal peptide synthetases. Nonribosomal peptides (NRPs) are of great pharmacological importance, but there is currently no technology for high-throughput NRP 'dereplication' and sequencing. We used multistage mass spectrometry followed by spectral alignment algorithms for sequencing of cyclic NRPs. We also developed an algorithm for comparative NRP dereplication that establishes similarities between newly isolated and previously identified similar but nonidentical NRPs, substantially reducing dereplication efforts.