8-Demethyl-8-dimethylaminoriboflavin (Roseoflavin or
RoF) is a
natural riboflavin analogue found in Streptomyces davaonensis and Streptomyces cinnabarinus. RoF
displays potent antibiotic properties because it affects FMN riboswitches
and flavoproteins of cellular targets. N,N-8-Demethyl-8-aminoriboflavin dimethyltransferase (RosA)
is an enzyme that catalyzes the last step of RoF biosynthesis, a consecutive
dimethylation of 8-demethyl-8-aminoriboflavin (AF) to generate RoF.
Thus, understanding mechanistic insights into RosA structures and
mechanisms could lead to the improvement of the RoF product yield.
Herein, mechanistic insights into roseoflavin synthesis by RosA were
evaluated using molecular dynamics simulations. The obtained results
revealed that RosA possibly catalyzes the reaction by positioning
the substrate binding to have proper distance and orientation to the
methyl group donor, S-adenosylmethionine. No direct participation
of catalytic residues in the reaction was identified. The enzyme’s
active site structures change drastically to accommodate the ligand
binding. On the basis of the MM/GBSA calculations and conservation
analysis, the amino acid residues involved in substrate binding were
identified. The structural information obtained from this study could
be beneficial in designing RosA to efficiently produce roseoflavin.