Tracking carrier protein motions with Raman spectroscopy

Nat Commun. 2019 May 20;10(1):2227. doi: 10.1038/s41467-019-10184-2.


Engineering microbial biosynthetic pathways represents a compelling route to gain access to expanded chemical diversity. Carrier proteins (CPs) play a central role in biosynthesis, but the fast motions of CPs make their conformational dynamics difficult to capture using traditional spectroscopic approaches. Here we present a low-resource method to directly reveal carrier protein-substrate interactions. Chemoenzymatic loading of commercially available, alkyne-containing substrates onto CPs enables rapid visualization of the molecular cargo's local environment using Raman spectroscopy. This method could clarify the foundations of the chain sequestration mechanism, facilitate the rapid characterization of CPs, and enable visualization of the vectoral processing of natural products both in vitro and in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacteria / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Biological Products / chemistry
  • Biological Products / metabolism*
  • Biosynthetic Pathways
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Metabolic Engineering
  • Protein Conformation
  • Spectrum Analysis, Raman / methods*


  • Bacterial Proteins
  • Biological Products
  • Carrier Proteins