title: Modern mass spectrometry for synthetic biology and structure-based discovery of natural products.
abstract: Covering: up to 2016In this highlight, we describe the current landscape for dereplication and discovery of natural products based on the measurement of the intact mass by LC-MS. Often it is assumed that because better mass accuracy (provided by higher resolution mass spectrometers) is necessary for absolute chemical formula determination (≤1 part-per-million), that it is also necessary for dereplication of natural products. However, the average ability to dereplicate tapers off at ∼10 ppm, with modest improvement gained from better mass accuracy when querying focused databases of natural products. We also highlight some recent examples of how these platforms are applied to synthetic biology, and recent methods for dereplication and correlation of substructures using tandem MS data. We also offer this highlight to serve as a brief primer for those entering the field of mass spectrometry-based natural products discovery.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. n-kelleher@northwestern.edu.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Henke
authors.forename: Neil L
authors.initials: NL
authors.lastname: Kelleher
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods; D016208:Databases, Factual; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D008970:Molecular Weight; D058615:Synthetic Biology
chemical_list: D001688:Biological Products