Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning

Jianjun Zhang; Ryan R. Hughes; Meredith A. Saunders; Sherif I. Elshahawi; Larissa V. Ponomareva; Yinan Zhang; Sydney R. Winchester; Samantha A. Scott; Manjula Sunkara; Andrew J. Morris; Mark A. Prendergast; Khaled A. Shaaban; Jon S. Thorson

doi:10.1021/acs.jnatprod.6b00949

Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning

Jianjun Zhang, Ryan R. Hughes, Meredith A. Saunders, Sherif I. Elshahawi, Larissa V. Ponomareva, Yinan Zhang, Sydney R. Winchester, Samantha A. Scott, Manjula Sunkara, Andrew J. Morris, Mark A. Prendergast, Khaled A. Shaaban, Jon S. Thorson

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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-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.

Original language	English
Pages (from-to)	12-18
Number of pages	7
Journal	Journal of Natural Products
Volume	80
Issue number	1
DOIs	https://doi.org/10.1021/acs.jnatprod.6b00949
State	Published - Jan 27 2017

Bibliographical note

Funding Information:
This work was supported in part by NIH R37 AI52188, NIH T32 DA016176 (YZ), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, and the National Center for Advancing Translational Sciences (UL1TR001998).

Publisher Copyright:
© 2016 American Chemical Society and American Society of Pharmacognosy.

ASJC Scopus subject areas

Analytical Chemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

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10.1021/acs.jnatprod.6b00949

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Zhang, J., Hughes, R. R., Saunders, M. A., Elshahawi, S. I., Ponomareva, L. V., Zhang, Y., Winchester, S. R., Scott, S. A., Sunkara, M., Morris, A. J., Prendergast, M. A., Shaaban, K. A., & Thorson, J. S. (2017). Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning. Journal of Natural Products, 80(1), 12-18. https://doi.org/10.1021/acs.jnatprod.6b00949

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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-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.",

author = "Jianjun Zhang and Hughes, {Ryan R.} and Saunders, {Meredith A.} and Elshahawi, {Sherif I.} and Ponomareva, {Larissa V.} and Yinan Zhang and Winchester, {Sydney R.} and Scott, {Samantha A.} and Manjula Sunkara and Morris, {Andrew J.} and Prendergast, {Mark A.} and Shaaban, {Khaled A.} and Thorson, {Jon S.}",

note = "Funding Information: This work was supported in part by NIH R37 AI52188, NIH T32 DA016176 (YZ), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, and the National Center for Advancing Translational Sciences (UL1TR001998). Publisher Copyright: {\textcopyright} 2016 American Chemical Society and American Society of Pharmacognosy.",

year = "2017",

month = jan,

day = "27",

doi = "10.1021/acs.jnatprod.6b00949",

language = "English",

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Zhang, J, Hughes, RR, Saunders, MA, Elshahawi, SI, Ponomareva, LV, Zhang, Y, Winchester, SR, Scott, SA, Sunkara, M, Morris, AJ, Prendergast, MA , Shaaban, KA & Thorson, JS 2017, 'Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning', Journal of Natural Products, vol. 80, no. 1, pp. 12-18. https://doi.org/10.1021/acs.jnatprod.6b00949

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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 - Funding Information: This work was supported in part by NIH R37 AI52188, NIH T32 DA016176 (YZ), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, and the National Center for Advancing Translational Sciences (UL1TR001998). 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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Identification of neuroprotective spoxazomicin and oxachelin glycosides via chemoenzymatic glycosyl-scanning

Abstract

Bibliographical note

ASJC Scopus subject areas

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