Metabolic glycoengineering of sialic acids

Jian Du, Ruben T. Almaraz, Elaine Tan, Kevin J Yarema

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Metabolic glycoengineering (MGE) refers to methodology developed over the last two decades wherein non-natural analogs of N-acetylmannosamine (ManNAc) intercept the biosynthetic pathway for sialic acid (Sia) in living cells and animals and subsequently become metabolically incorporated into sialoglycoconjugates in place of the natural sialosides. This article provides an overview of this technology by describing the chemical diversity that can be installed into cell surface sugars and can be subsequently exploited for numerous applications that include glycan labeling, glycomics, and -potentially-therapies for many disorders and diseases in which Sia play a role. Translation of metabolic glycoengineering from the laboratory to the clinic, however, faces substantial obstacles including the poor bioavailability of ManNAc analogs at both the cell and systemic levels. These issues are being addressed through the use of short chain fatty acid (SCFA)-monosaccharide hybrid molecules which, in addition to more favorable pharmacological properties, also harbor new modes of biological activity that present both pitfalls and new opportunities for burgeoning MGE technology.

Original languageEnglish (US)
Title of host publicationSialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease
PublisherBentham Science Publishers Ltd
Pages476-511
Number of pages36
ISBN (Print)9781608050673
DOIs
StatePublished - 2013

Fingerprint

Sialic Acids
N-Acetylneuraminic Acid
Volatile Fatty Acids
Monosaccharides
Ports and harbors
Bioactivity
Sugars
Glycomics
Labeling
Technology
Polysaccharides
Animals
Biosynthetic Pathways
Cells
Biological Availability
Molecules
Pharmacology
Therapeutics
N-acetylmannosamine

Keywords

  • Cancer
  • CMP-sialic acid analogs
  • Glycosylation machinery
  • Metabolic glycoengineering
  • N-Acetylgalactosamine analogs
  • N-Acetylglucosamine analogs
  • N-Acetylmannosamine analogs
  • Short chain fatty acid (SCFA)-monosaccharides
  • Sialic acid analogs
  • Sialic acid biorthogonal functionality
  • Sialic acids
  • Tissue engineering

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Du, J., Almaraz, R. T., Tan, E., & Yarema, K. J. (2013). Metabolic glycoengineering of sialic acids. In Sialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease (pp. 476-511). Bentham Science Publishers Ltd. https://doi.org/10.2174/9781608053865113010017

Metabolic glycoengineering of sialic acids. / Du, Jian; Almaraz, Ruben T.; Tan, Elaine; Yarema, Kevin J.

Sialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease. Bentham Science Publishers Ltd, 2013. p. 476-511.

Research output: Chapter in Book/Report/Conference proceedingChapter

Du, J, Almaraz, RT, Tan, E & Yarema, KJ 2013, Metabolic glycoengineering of sialic acids. in Sialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease. Bentham Science Publishers Ltd, pp. 476-511. https://doi.org/10.2174/9781608053865113010017
Du J, Almaraz RT, Tan E, Yarema KJ. Metabolic glycoengineering of sialic acids. In Sialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease. Bentham Science Publishers Ltd. 2013. p. 476-511 https://doi.org/10.2174/9781608053865113010017
Du, Jian ; Almaraz, Ruben T. ; Tan, Elaine ; Yarema, Kevin J. / Metabolic glycoengineering of sialic acids. Sialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease. Bentham Science Publishers Ltd, 2013. pp. 476-511
@inbook{ca4afc47df364dd7a3b86da5bba619cb,
title = "Metabolic glycoengineering of sialic acids",
abstract = "Metabolic glycoengineering (MGE) refers to methodology developed over the last two decades wherein non-natural analogs of N-acetylmannosamine (ManNAc) intercept the biosynthetic pathway for sialic acid (Sia) in living cells and animals and subsequently become metabolically incorporated into sialoglycoconjugates in place of the natural sialosides. This article provides an overview of this technology by describing the chemical diversity that can be installed into cell surface sugars and can be subsequently exploited for numerous applications that include glycan labeling, glycomics, and -potentially-therapies for many disorders and diseases in which Sia play a role. Translation of metabolic glycoengineering from the laboratory to the clinic, however, faces substantial obstacles including the poor bioavailability of ManNAc analogs at both the cell and systemic levels. These issues are being addressed through the use of short chain fatty acid (SCFA)-monosaccharide hybrid molecules which, in addition to more favorable pharmacological properties, also harbor new modes of biological activity that present both pitfalls and new opportunities for burgeoning MGE technology.",
keywords = "Cancer, CMP-sialic acid analogs, Glycosylation machinery, Metabolic glycoengineering, N-Acetylgalactosamine analogs, N-Acetylglucosamine analogs, N-Acetylmannosamine analogs, Short chain fatty acid (SCFA)-monosaccharides, Sialic acid analogs, Sialic acid biorthogonal functionality, Sialic acids, Tissue engineering",
author = "Jian Du and Almaraz, {Ruben T.} and Elaine Tan and Yarema, {Kevin J}",
year = "2013",
doi = "10.2174/9781608053865113010017",
language = "English (US)",
isbn = "9781608050673",
pages = "476--511",
booktitle = "Sialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease",
publisher = "Bentham Science Publishers Ltd",

}

TY - CHAP

T1 - Metabolic glycoengineering of sialic acids

AU - Du, Jian

AU - Almaraz, Ruben T.

AU - Tan, Elaine

AU - Yarema, Kevin J

PY - 2013

Y1 - 2013

N2 - Metabolic glycoengineering (MGE) refers to methodology developed over the last two decades wherein non-natural analogs of N-acetylmannosamine (ManNAc) intercept the biosynthetic pathway for sialic acid (Sia) in living cells and animals and subsequently become metabolically incorporated into sialoglycoconjugates in place of the natural sialosides. This article provides an overview of this technology by describing the chemical diversity that can be installed into cell surface sugars and can be subsequently exploited for numerous applications that include glycan labeling, glycomics, and -potentially-therapies for many disorders and diseases in which Sia play a role. Translation of metabolic glycoengineering from the laboratory to the clinic, however, faces substantial obstacles including the poor bioavailability of ManNAc analogs at both the cell and systemic levels. These issues are being addressed through the use of short chain fatty acid (SCFA)-monosaccharide hybrid molecules which, in addition to more favorable pharmacological properties, also harbor new modes of biological activity that present both pitfalls and new opportunities for burgeoning MGE technology.

AB - Metabolic glycoengineering (MGE) refers to methodology developed over the last two decades wherein non-natural analogs of N-acetylmannosamine (ManNAc) intercept the biosynthetic pathway for sialic acid (Sia) in living cells and animals and subsequently become metabolically incorporated into sialoglycoconjugates in place of the natural sialosides. This article provides an overview of this technology by describing the chemical diversity that can be installed into cell surface sugars and can be subsequently exploited for numerous applications that include glycan labeling, glycomics, and -potentially-therapies for many disorders and diseases in which Sia play a role. Translation of metabolic glycoengineering from the laboratory to the clinic, however, faces substantial obstacles including the poor bioavailability of ManNAc analogs at both the cell and systemic levels. These issues are being addressed through the use of short chain fatty acid (SCFA)-monosaccharide hybrid molecules which, in addition to more favorable pharmacological properties, also harbor new modes of biological activity that present both pitfalls and new opportunities for burgeoning MGE technology.

KW - Cancer

KW - CMP-sialic acid analogs

KW - Glycosylation machinery

KW - Metabolic glycoengineering

KW - N-Acetylgalactosamine analogs

KW - N-Acetylglucosamine analogs

KW - N-Acetylmannosamine analogs

KW - Short chain fatty acid (SCFA)-monosaccharides

KW - Sialic acid analogs

KW - Sialic acid biorthogonal functionality

KW - Sialic acids

KW - Tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=84882602518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882602518&partnerID=8YFLogxK

U2 - 10.2174/9781608053865113010017

DO - 10.2174/9781608053865113010017

M3 - Chapter

AN - SCOPUS:84882602518

SN - 9781608050673

SP - 476

EP - 511

BT - Sialobiology: Structure, Biosynthesis and Function. Sialic Acid Glycoconjugates in Health and Disease

PB - Bentham Science Publishers Ltd

ER -