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

Producción científica: Article › revisión exhaustiva

7 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	12-18
Número de páginas	7
Publicación	Journal of Natural Products
Volumen	80
N.º	1
DOI	https://doi.org/10.1021/acs.jnatprod.6b00949
Estado	Published - ene 27 2017

Nota bibliográfica

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

Financiación

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).

Financiadores	Número del financiador
University of Kentucky
National Institutes of Health (NIH)	R37 AI52188
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse	T32DA016176
National Center for Advancing Translational Sciences (NCATS)	UL1TR001998
University of Kentucky Markey Comprehensive Cancer Center

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 = "Publisher Copyright: {\textcopyright} 2016 American Chemical Society and American Society of Pharmacognosy.",

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

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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, n.º 1, pp. 12-18. https://doi.org/10.1021/acs.jnatprod.6b00949

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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.

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

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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