Fluorometric Analysis of Carrier-Protein-Dependent Biosynthesis through a Conformationally Sensitive Solvatochromic Pantetheinamide Probe

ACS Chem Biol. 2024 Jul 19;19(7):1416-1425. doi: 10.1021/acschembio.4c00169. Epub 2024 Jun 23.

Abstract

Carrier proteins (CPs) play a fundamental role in the biosynthesis of fatty acids, polyketides, and non-ribosomal peptides, encompassing many medicinally and pharmacologically relevant compounds. Current approaches to analyze novel carrier-protein-dependent synthetic pathways are hampered by a lack of activity-based assays for natural product biosynthesis. To fill this gap, we turned to 3-methoxychromones, highly solvatochromic fluorescent molecules whose emission intensity and wavelength are heavily dependent on their immediate molecular environment. We have developed a solvatochromic carrier-protein-targeting probe which is able to selectively fluoresce when bound to a target carrier protein. Additionally, the probe displays distinct responses upon CP binding in carrier-protein-dependent synthases. This discerning approach demonstrates the design of solvatochromic fluorophores with the ability to identify biosynthetically active CP-enzyme interactions.

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Fluorescent Dyes* / chemistry
  • Fluorometry / methods
  • Pantetheine / analogs & derivatives
  • Pantetheine / chemistry
  • Pantetheine / metabolism

Substances

  • Fluorescent Dyes
  • Carrier Proteins
  • Pantetheine