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Updated: Jul 2, 2026

Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
Published on: March 12, 2020
Accessing natural product biosynthetic processes by mass spectrometry
Stefanie B Bumpus1, Neil L Kelleher
1Department of Chemistry & The Institute for Genomic Biology, University of Illinois Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
Abstract:
Two important classes of natural products are made by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). With most biosynthetic intermediates covalently tethered during biogenesis, protein mass spectrometry (MS) has proven invaluable for their interrogation. New mass spectrometric assay formats (such as selective cofactor ejection and proteomics style LC-MS) are showcased here in the context of functional insights into new breeds of NRPS/PKS enzymes, including the first characterization of an 'iterative' PKS, the biosynthesis of the enediyne antitumor antibiotics, the study of a new strategy for PKS initiation via a GNAT-like mechanism, and the analysis of branching strategies in the so-called 'AT-less' NRPS/PKS hybrid systems. The future of MS analysis of NRPS and PKS biosynthetic pathways lies in adoption and development of methods that continue bridging enzymology with proteomics as both fields continue their post-genomic acceleration.
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