Engineering fluorometabolite production: fluorinase expression in Salinispora tropica Yields Fluorosalinosporamide

J Nat Prod. 2010 Mar 26;73(3):378-82. doi: 10.1021/np900719u.

Abstract

Organofluorine compounds play an important role in medicinal chemistry, where they are responsible for up to 15% of the pharmaceutical products on the market. While natural products are valuable sources of new chemical entities, natural fluorinated molecules are extremely rare and the pharmaceutical industry has not benefited from a microbial source of this class of compounds. Streptomyces cattleya is an unusual bacterium in that it elaborates fluoroacetate and the amino acid 4-fluorothreonine. The discovery in 2002 of the fluorination enzyme FlA responsible for C-F bond formation in S. cattleya, and its subsequent characterization, opened up for the first time the prospect of genetically engineering fluorometabolite production from fluoride ion in host organisms. As a proof of principle, we report here the induced production of fluorosalinosporamide by replacing the chlorinase gene salL from Salinispora tropica with the fluorinase gene flA.

Publication types

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

MeSH terms

  • Actinobacteria / enzymology*
  • Actinobacteria / genetics
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Genetic Engineering
  • Hydrocarbons, Fluorinated / analysis*
  • Hydrocarbons, Fluorinated / chemistry
  • Lactones / analysis*
  • Lactones / chemistry
  • Molecular Structure
  • Organisms, Genetically Modified / metabolism*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Streptomyces / metabolism*

Substances

  • Bacterial Proteins
  • Hydrocarbons, Fluorinated
  • Lactones
  • fluorosalinosporamide
  • Oxidoreductases
  • fluorinase