title: Enzymatic synthesis of heparan sulfate and heparin.
abstract: Heparan sulfate (HS) polysaccharide chains have been shown to orchestrate distinct biological functions in several systems. Study of HS structure-function relations is, however, hampered due to the lack of availability of HS in sufficient quantities as well as the molecular heterogeneity of naturally occurring HS. Enzymatic synthesis of HS is an attractive alternative to the use of naturally occurring HS, as it reduces molecular heterogeneity, or a long and daunting chemical synthesis of HS. Heparosan, produced by E. coli K5 bacteria, has a structure similar to the unmodified HS backbone structure and can be used as a precursor in the enzymatic synthesis of HS-like polysaccharides. Here, we describe an enzymatic approach to synthesize several specifically sulfated HS polysaccharides for biological studies using the heparosan backbone and a combination of recombinant biosynthetic enzymes such as C5-epimerase and sulfotransferases.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Skaggs #307, Salt Lake City, UT, 84112, USA.
authors.forename: April
authors.initials: A
authors.lastname: Joice
authors.forename: Karthik
authors.initials: K
authors.lastname: Raman
authors.forename: Caitlin
authors.initials: C
authors.lastname: Mencio
authors.forename: Maritza V
authors.initials: MV
authors.lastname: Quintero
authors.forename: Spencer
authors.initials: S
authors.lastname: Brown
authors.forename: Thao Kim Nu
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Balagurunathan
authors.initials: B
authors.lastname: Kuberan
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000378:metabolism; D004798:Enzymes / Q000302:isolation & purification / Q000378:metabolism*; D006493:Heparin / Q000138:chemical synthesis* / Q000737:chemistry; D006497:Heparan Sulfate / Q000138:chemical synthesis* / Q000737:chemistry; D007474:Ion Exchange; D061987:Sf9 Cells; D015238:Sulfotransferases / Q000378:metabolism
chemical_list: D004187:Disaccharides; D004798:Enzymes; D006493:Heparin; D006497:Heparan Sulfate; D015238:Sulfotransferases; C560363:heparosan