Acceptor substrate determines donor specificity of an aromatic prenyltransferase: expanding the biocatalytic potential of NphB

• DOI: 10.1007/s00253-020-10529-8
• Publication Date: 2020-03-18T11:56:39Z
• Authors: Bryce P. Johnson; Erin M. Scull; Dustin A. Dimas; Tejaswi Bavineni; Chandrasekhar Ban...; Andrea L. Batchev; Eric D. Gardner; Susan L. Nimmo; Shanteri Singh
• Keywords: Prenyltransferase; Biocatalysis; Acceptor

Abstract Aromatic prenyltransferases are known for their extensive promiscuity toward aromatic acceptor substrates and ability to form various carbon-carbon carbon-heteroatom bonds. Of particular interest among the is NphB, whose geranylate cannabinoid precursors has been utilized in several vivo vitro systems. It therefore established that can be as biocatalysts generation of useful compounds. However, recent observations non-native alkyl-donor indicate role NphB biocatalysis could expanded beyond geranylation reactions. Therefore, goal this study was elucidate donor using different substrates. Herein, we report distinct profiles between NphB-catalyzed reactions involving substrate 1,6-dihydroxynaphthalene an FDA-approved drug molecule sulfabenzamide. Furthermore, first instance regiospecific, N -alkylation sulfabenzamide a library alkyl-donors, indicating biocatalytic potential late-stage diversification tool. Key Points • utilize antibacterial acceptor. The profile changes dramatically with choice performs previously unknown regiospecific N-alkylation on Prenyltransferases like drug-alkylating biocatalysts.