We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Acceptor substrate determines donor specificity of an aromatic prenyltransferase: expanding the biocatalytic potential of NphB.
- Authors
Johnson, Bryce P.; Scull, Erin M.; Dimas, Dustin A.; Bavineni, Tejaswi; Bandari, Chandrasekhar; Batchev, Andrea L.; Gardner, Eric D.; Nimmo, Susan L.; Singh, Shanteri
- Abstract
Aromatic prenyltransferases are known for their extensive promiscuity toward aromatic acceptor substrates and their ability to form various carbon-carbon and carbon-heteroatom bonds. Of particular interest among the prenyltransferases is NphB, whose ability to geranylate cannabinoid precursors has been utilized in several in vivo and in vitro systems. It has therefore been established that prenyltransferases can be utilized as biocatalysts for the generation of useful compounds. However, recent observations of non-native alkyl-donor promiscuity among prenyltransferases indicate the role of NphB in biocatalysis could be expanded beyond geranylation reactions. Therefore, the goal of this study was to elucidate the donor promiscuity of NphB using different acceptor substrates. Herein, we report distinct donor profiles between NphB-catalyzed reactions involving the known substrate 1,6-dihydroxynaphthalene and an FDA-approved drug molecule sulfabenzamide. Furthermore, we report the first instance of regiospecific, NphB-catalyzed N-alkylation of sulfabenzamide using a library of non-native alkyl-donors, indicating the biocatalytic potential of NphB as a late-stage diversification tool. Key Points: • NphB can utilize the antibacterial drug sulfabenzamide as an acceptor. • The donor profile of NphB changes dramatically with the choice of acceptor. • NphB performs a previously unknown regiospecific N-alkylation on sulfabenzamide. • Prenyltransferases like NphB can be utilized as drug-alkylating biocatalysts.
- Subjects
UNITED States. Food &; Drug Administration; DIMETHYLALLYLTRANSTRANSFERASE; CARBON-carbon bonds; ENZYMES; BIOCATALYSIS
- Publication
Applied Microbiology & Biotechnology, 2020, Vol 104, Issue 10, p4383
- ISSN
0175-7598
- Publication type
Article
- DOI
10.1007/s00253-020-10529-8