De novo Sequencing of nonribosomal peptides

While nonribosomal peptides (NRPs) are of tremendous pharmacological importance, there is currently no technology capable of high-throughput sequencing of NRPs. Difficulties in sequencing NRPs slow down the progress in elucidating the non-ribosomal genetic code and negatively affect various screening programs aimed at the discovery of natural compounds of medical importance. We propose to employ multi-stage mass-spectrometry (MSn) for the data acquisition, followed by alignment-based heuristic algorithms for data analysis. Since mass spectrometry based analysis of NRPs is fast and inexpensive, this approach opens the possibility of high-throughput sequencing of many unknown NRPs accumulated in large screening programs.