Predicting the substrate scope of the flavin-dependent halogenase BrvH by virtual screening.
Scientists at IPB and the University of Bielefeld recently identified previously unknown substrates of the flavin-dependent halogenase BrvH. Some halogenated compounds are bioactive and therefore interesting for drug discovery.
Based on an X-ray structure, the researchers generated a computer model of BrvH. With known substrates of BrvH, they analyzed parameters, like distance, partial charge, and hybridization state, to derive rules for prediction of activity. Using these parameters, the scientist performed a virtual screening of compound databases and identified numerous potential substrates. Subsequent in vitro tests confirmed several candidates as previously unknown substrates of BrvH.
Insights into the structure-activity relationship and substrate binding of BrvH may facilitate the discovery of unknown natural products that could serve as precursor for the production of halogenated drugs. This approach could provide a green alternative to the harsh reaction conditions of chemical halogenation.
Reference:
Neubauer PR, Pienkny S, Wessjohann LA, Brandt W, Sewald N. Predicting the substrate scope of the flavin-dependent halogenase BrvH [published online ahead of print, 2020 Jul 9]. Chembiochem. 2020;10.1002/cbic.202000444. doi:10.1002/cbic.202000444
