Identification of the Key Enzyme of Roseoflavin Biosynthesis

Angew Chem Int Ed Engl. 2016 May 10;55(20):6103-6. doi: 10.1002/anie.201600581. Epub 2016 Apr 9.

Abstract

The bacteria Streptomyces davawensis and Streptomyces cinnabarinus produce roseoflavin, the only known natural riboflavin (vitamin B2 ) analogue with antibiotic activity. Roseoflavin can be considered a natural antimetabolite and has been postulated to be biosynthesized from riboflavin via the key intermediate 8-demethyl-8-aminoriboflavin (AF). The required site-specific substitution of one of the methyl groups on the dimethylbenzene ring of riboflavin by an amino group (to give AF) is challenging. The pathway from riboflavin to AF has remained elusive, and the corresponding enzyme/s was/were unknown. Herein, we show by systematic gene deletion, heterologous gene expression, and biochemical studies that the enzyme specified by the gene BN159_7989 from S. davawensis is able to carry out a whole set of chemical reactions starting from riboflavin-5'-phosphate to give the final product 8-demethyl-8-aminoriboflavin-5'-phosphate (AFP).

Keywords: riboflavin; riboflavin-5′-phosphate; roseoflavin; streptomyces davawensis.

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Mass Spectrometry
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Plasmids / genetics
  • Plasmids / metabolism
  • Riboflavin / analogs & derivatives*
  • Riboflavin / biosynthesis
  • Riboflavin / chemistry
  • Riboflavin / metabolism
  • Streptomyces / enzymology
  • Streptomyces / genetics

Substances

  • Bacterial Proteins
  • roseoflavin
  • 8-amino-8-demethylriboflavin
  • Methyltransferases
  • Phosphotransferases (Alcohol Group Acceptor)
  • riboflavin kinase
  • Riboflavin