title: Biosynthesis of UDP-4-keto-6-deoxyglucose and UDP-rhamnose in pathogenic fungi Magnaporthe grisea and Botryotinia fuckeliana.
abstract: There is increasing evidence that in several fungi, rhamnose-containing glycans are involved in processes that affect host-pathogen interactions, including adhesion, recognition, virulence, and biofilm formation. Nevertheless, little is known about the pathways for the synthesis of these glycans. We show that rhamnose is present in glycans isolated from the rice pathogen Magnaporthe grisea and from the plant pathogen Botryotinia fuckeliana. We also provide evidence that these fungi produce UDP-rhamnose. This is in contrast to bacteria where dTDP-rhamnose is the activated form of this sugar. In bacteria, formation of dTDP-rhamnose requires three enzymes. Here, we demonstrate that in fungi only two genes are required for UDP-Rha synthesis. The first gene encodes a UDP-glucose-4,6-dehydratase that converts UDP-glucose to UDP-4-keto-6-deoxyglucose. The product was shown by time-resolved (1)H NMR spectroscopy to exist in solution predominantly as a hydrated form along with minor amounts of a keto form. The second gene encodes a bifunctional UDP-4-keto-6-deoxyglucose-3,5-epimerase/-4-reductase that converts UDP-4-keto-6-deoxyglucose to UDP-rhamnose. Sugar composition analysis and gene expression studies at different stages of growth indicate that the synthesis of rhamnose-containing glycans is under tissue-specific regulation. Together, our results provide new insight into the formation of rhamnose-containing glycans during the fungal life cycle. The role of these glycans in the interactions between fungal pathogens and their hosts is discussed. Knowledge of the metabolic pathways involved in the formation of rhamnose-containing glycans may facilitate the development of drugs to combat fungal diseases in humans, as to the best of our knowledge mammals do not make these types of glycans.
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Viviana
authors.initials: V
authors.lastname: Martinez
authors.forename: Miles
authors.initials: M
authors.lastname: Ingwers
authors.forename: James
authors.initials: J
authors.lastname: Smith
authors.forename: John
authors.initials: J
authors.lastname: Glushka
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Maor
authors.initials: M
authors.lastname: Bar-Peled
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D005800:Genes, Fungal / Q000502:physiology*; D005947:Glucose / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D020082:Magnaporthe / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D010935:Plant Diseases / Q000235:genetics / Q000382:microbiology; D014530:Uridine Diphosphate / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D014539:Uridine Diphosphate Sugars / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C115446:UDP-4-keto-6-deoxyglucose; D014539:Uridine Diphosphate Sugars; C022183:UDP-rhamnose; D014530:Uridine Diphosphate; D005947:Glucose
references.citation: Eukaryot Cell. 2007 Aug;6(8):1450-63
references.pmid: 17557881
references.citation: J Biol Chem. 2009 Aug 7;284(32):21526-35
references.pmid: 19509290
references.citation: FEBS J. 2009 Jul;276(14):3698-709
references.pmid: 19496815
references.citation: Biochemistry. 2002 Feb 26;41(8):2797-804
references.pmid: 11851427
references.citation: J Mol Biol. 2001 Mar 16;307(1):283-95
references.pmid: 11243820
references.citation: J Mol Biol. 2007 Jan 5;365(1):146-59
references.pmid: 17046787
references.citation: J Am Chem Soc. 2003 Oct 1;125(39):11872-8
references.pmid: 14505409
references.citation: J Gen Microbiol. 1969 Nov;58(3):307-15
references.pmid: 5365925
references.citation: J Biol Chem. 2005 Jun 17;280(24):23000-8
references.pmid: 15809294
references.citation: J Bacteriol. 2010 Oct;192(19):5053-62
references.pmid: 20675481
references.citation: Science. 1988 Jan 15;239(4837):288-90
references.pmid: 17769992
references.citation: J Bacteriol. 2002 Jun;184(12):3392-5
references.pmid: 12029057
references.citation: Philos Trans R Soc Lond B Biol Sci. 2001 Jul 29;356(1411):983-9
references.pmid: 11516376
references.citation: Curr Opin Plant Biol. 2010 Aug;13(4):434-41
references.pmid: 20627803
references.citation: J Biol Chem. 2010 Aug 6;285(32):24825-33
references.pmid: 20529859
references.citation: Plant Physiol. 2004 Apr;134(4):1337-46
references.pmid: 15020741
references.citation: Annu Rev Phytopathol. 2005;43:205-27
references.pmid: 16078883
references.citation: J Appl Microbiol. 2010 Jul;109(1):128-36
references.pmid: 20002865
references.citation: Carbohydr Res. 2002 Oct 11;337(19):1707-13
references.pmid: 12423948
references.citation: Med Mycol. 2009 Mar;47(2):185-96
references.pmid: 18608892
references.citation: Mycopathologia. 1995 Nov;132(2):71-7
references.pmid: 8819829
references.citation: Nature. 2007 Apr 26;446(7139):1008-16
references.pmid: 17460661
references.citation: Carbohydr Res. 2004 Nov 15;339(16):2667-71
references.pmid: 15519325
references.citation: Fungal Genet Biol. 1999 Jul-Aug;27(2-3):186-98
references.pmid: 10441444
references.citation: Fungal Genet Biol. 1996 Jun;20(2):115-24
references.pmid: 8810516
references.citation: J Biol Chem. 2007 Feb 23;282(8):5389-403
references.pmid: 17190829
references.citation: Carbohydr Res. 2006 Apr 10;341(5):645-9
references.pmid: 16442515
references.citation: Structure. 2002 Jan;10(1):81-92
references.pmid: 11796113
references.citation: J Virol. 2010 Sep;84(17):8829-38
references.pmid: 20538863