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Evolution of a New Pathway of Reserve Carbohydrate Biosynthesis in Leishmania Parasites

79 Pages Posted: 14 May 2019 Publication Status: Published

See all articles by Fleur Sernee

Fleur Sernee

University of Melbourne - Department of Biochemistry and Molecular Biology

Julie Ralton

University of Melbourne - Department of Biochemistry and Molecular Biology

Tracy L. Nero

University of Melbourne - Department of Biochemistry and Molecular Biology

Lukasz Sobala

University of York - Department of Chemistry

Marcel Viera-Lara

University of Melbourne - Department of Biochemistry and Molecular Biology

Joachim Kloehn

University of Melbourne - Department of Biochemistry and Molecular Biology

Simon Cobbold

University of Melbourne - Department of Biochemistry and Molecular Biology

Lauren Stanton

University of Melbourne - Department of Biochemistry and Molecular Biology

Douglas E.V. Pires

University of Melbourne - Department of Biochemistry and Molecular Biology

Eric Hanssen

University of Melbourne - Department of Biochemistry and Molecular Biology

Alexandra Males

University of York - Department of Chemistry

Tom Ward

University of York - Department of Chemistry

Laurence M. Bastidas

University of York - Department of Chemistry

Phillip L. van der Peet

University of Melbourne - School of Chemistry

Michael W. Parker

University of Melbourne - Department of Biochemistry and Molecular Biology

David B. Ascher

University of Melbourne - Department of Biochemistry and Molecular Biology

Spencer J. Williams

University of Melbourne - School of Chemistry

Gideon Davies

University of York - Department of Chemistry

Malcolm McConville

University of Melbourne - Department of Biochemistry and Molecular Biology

More...

Abstract

Leishmania are medically important protozoan parasites that have replaced canonical pathways of reserve carbohydrate biosynthesis with a new pathway for synthesis of β-1,2-mannan oligosaccharides, termed mannogen. Here we describe a new class of enzymes that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. These dual activity mannosyltransferases/phosphorylases (MTPs) are structurally related to bacterial mannan phosphorylases, but constitute a new family of glycosyltransferases (GTXXX) that have been acquired by horizontal transfer from gram-positive bacteria. The MTPs catalyze the constitutive turnover of mannogen, which protects obligate intracellular parasite stages from nutrient excess and is essential for thermotolerance and infectivity in the mammalian host. These studies reveal a primordial function for reserve carbohydrates as dynamic metabolic rheostats and highlight the role of metabolic evolution in allowing these protists to colonize new host niches.

Keywords: parasite pathogenesis, central carbon metabolism, horizontal gene transfer, glycan phosphorylase, glycosyltransferase, carbohydrate reserve, mannan, X-ray crystallography

Suggested Citation

Sernee, Fleur and Ralton, Julie and Nero, Tracy L. and Sobala, Lukasz and Viera-Lara, Marcel and Kloehn, Joachim and Cobbold, Simon and Stanton, Lauren and Pires, Douglas E.V. and Hanssen, Eric and Males, Alexandra and Ward, Tom and Bastidas, Laurence M. and van der Peet, Phillip L. and Parker, Michael W. and Ascher, David B. and Williams, Spencer J. and Davies, Gideon and McConville, Malcolm, Evolution of a New Pathway of Reserve Carbohydrate Biosynthesis in Leishmania Parasites (May 4, 2019). Available at SSRN: https://ssrn.com/abstract=3382549 or http://dx.doi.org/10.2139/ssrn.3382549
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Fleur Sernee

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Julie Ralton

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Tracy L. Nero

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Lukasz Sobala

University of York - Department of Chemistry

United Kingdom

Marcel Viera-Lara

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Joachim Kloehn

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Simon Cobbold

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Lauren Stanton

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Douglas E.V. Pires

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Eric Hanssen

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Alexandra Males

University of York - Department of Chemistry

United Kingdom

Tom Ward

University of York - Department of Chemistry

United Kingdom

Laurence M. Bastidas

University of York - Department of Chemistry

United Kingdom

Phillip L. Van der Peet

University of Melbourne - School of Chemistry

Australia

Michael W. Parker

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

David B. Ascher

University of Melbourne - Department of Biochemistry and Molecular Biology

Australia

Spencer J. Williams

University of Melbourne - School of Chemistry

Australia

Gideon Davies

University of York - Department of Chemistry

United Kingdom

Malcolm McConville (Contact Author)

University of Melbourne - Department of Biochemistry and Molecular Biology ( email )

Australia

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