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Identification of the Key Enzyme of Roseoflavin Biosynthesis
Author(s) -
Schwarz Julia,
Konjik Valentino,
Jankowitsch Frank,
Sandhoff Roger,
Mack Matthias
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201600581
Subject(s) - riboflavin , enzyme , biochemistry , streptomyces , heterologous expression , gene , biosynthesis , bacteria , biology , heterologous , chemistry , recombinant dna , genetics
The bacteria Streptomyces davawensis and Streptomyces cinnabarinus produce roseoflavin, the only known natural riboflavin (vitamin B 2 ) 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).