This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including daptomycin. Two additional PTs also produced novel prenylated daptomycins with improved antibacterial activities over the parent drug.
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This work was supported by NIH grants R37 AI52188 and R01 CA203257 (J.S.T.), U01 GM098248 (G.N.P.) and NCATS (UL1TR001998).
Supplementary information and chemical compound information is available online at http://www.nature.com/naturechemicalbiology/.
Nucleotide sequence data for pri cluster is available under GenBank accession code KT895008. The PriB X-ray crystal structures were deposited at the Protein Database Bank: PriB/L-Trp/dimethylallyl S-thiolodiphosphate ternary complex (5INJ), the apo structure (5JXM), and the PriB/pyrophosphate binary complex (5K9M). All other data generated or analyzed during this study are included in this published article (and its supplementary information files) or are available from the corresponding author on reasonable request.
Elshahawi, Sherif I.; Cao, Hongnan; Shaaban, Khaled A.; Ponomareva, Larissa V.; Subramanian, Thangaiah; Farman, Mark L.; Spielmann, H. Peter; Phillips, George N. Jr.; Thorson, Jon S.; and Singh, Shanteri, "Structure and Specificity of a Permissive Bacterial C-Prenyltransferase" (2017). Pharmaceutical Sciences Faculty Publications. 134.