Evolution of a New Pathway of Reserve Carbohydrate Biosynthesis in Leishmania Parasites
79 Pages Posted: 14 May 2019 Publication Status: PublishedMore...
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
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