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

7 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

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

Funding

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).

Funders	Funder number
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

Access to Document

10.1021/acs.jnatprod.6b00949

Cite this

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

@article{d4f9d4981d2a4c8fad55b26d26e70c23,

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.",

year = "2017",

month = jan,

day = "27",

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

language = "English",

volume = "80",

pages = "12--18",

number = "1",

}

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

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85011110753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011110753&partnerID=8YFLogxK

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 -

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this