title: Identification of Neuroprotective Spoxazomicin and Oxachelin Glycosides via Chemoenzymatic Glycosyl-Scanning.
abstract: The assessment of glycosyl-scanning to expand the molecular and functional diversity of metabolites from the underground coal mine fire-associated Streptomyces sp. RM-14-6 is reported. Using the engineered glycosyltransferase OleD Loki and a 2-chloro-4-nitrophenylglycoside-based screen, six metabolites were identified as substrates of OleD Loki, from which 12 corresponding metabolite glycosides were produced and characterized. This study highlights the first application of the 2-chloro-4-nitrophenylglycoside-based screen toward an unbiased set of unique microbial natural products and the first reported application of the 2-chloro-4-nitrophenylglycoside-based transglycosylation reaction for the corresponding preparative synthesis of target glycosides. Bioactivity analysis (including antibacterial, antifungal, anticancer, and EtOH damage neuroprotection assays) revealed glycosylation to attenuate the neuroprotective potency of 4, while glycosylation of the structurally related inactive spoxazomicin C (3) remarkably invoked neuroprotective activity.
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Hughes
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Saunders
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Sherif I
authors.initials: SI
authors.lastname: Elshahawi
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Ponomareva
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Sydney R
authors.initials: SR
authors.lastname: Winchester
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Scott
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Prendergast
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Shaaban
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, ‡Department of Pharmaceutical Sciences, College of Pharmacy, §Department of Psychology and Spinal Cord and Brain Injury Research Center, and ∥Division of Cardiovascular Medicine, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Jon S
authors.identifier: 0000-0002-7148-0721
authors.initials: JS
authors.lastname: Thorson
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry*; D006031:Glycosylation; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010080:Oxazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D006027:Glycosides; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010080:Oxazoles; C516693:oxachelin; C558841:spoxazomicin C