TY - JOUR
T1 - Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning
AU - Zhang, Jianjun
AU - Hughes, Ryan R.
AU - Saunders, Meredith A.
AU - Elshahawi, Sherif I.
AU - Ponomareva, Larissa V.
AU - Zhang, Yinan
AU - Winchester, Sydney R.
AU - Scott, Samantha A.
AU - Sunkara, Manjula
AU - Morris, Andrew J.
AU - Prendergast, Mark A.
AU - Shaaban, Khaled A.
AU - Thorson, Jon S.
N1 - Publisher Copyright:
© 2016 American Chemical Society and American Society of Pharmacognosy.
PY - 2017/1/27
Y1 - 2017/1/27
N2 - 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-nitrophenylglycosidebased 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.
AB - 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-nitrophenylglycosidebased 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.
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U2 - 10.1021/acs.jnatprod.6b00949
DO - 10.1021/acs.jnatprod.6b00949
M3 - Article
C2 - 28029796
AN - SCOPUS:85011110753
SN - 0163-3864
VL - 80
SP - 12
EP - 18
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 1
ER -