title: Combinatorial biosynthesis of antitumor deoxysugar pathways in Streptomyces griseus: Reconstitution of "unnatural natural gene clusters" for the biosynthesis of four 2,6-D-dideoxyhexoses.
abstract: Combinatorial biosynthesis was applied to Streptomyces deoxysugar biosynthesis genes in order to reconstitute "unnatural natural gene clusters" for the biosynthesis of four D-deoxysugars (D-olivose, D-oliose, D-digitoxose, and D-boivinose). Expression of these gene clusters in Streptomyces albus 16F4 was used to prove the functionality of the designed clusters through the generation of glycosylated tetracenomycins. Three glycosylated tetracenomycins were generated and characterized, two of which (D-digitoxosyl-tetracenomycin C and D-boivinosyl-tetracenocmycin C) were novel compounds. The constructed gene clusters may be used to increase the capabilities of microorganisms to synthesize new deoxysugars and therefore to produce new glycosylated bioactive compounds.
authors.affiliation: Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, Oviedo, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pérez
authors.forename: Felipe
authors.initials: F
authors.lastname: Lombó
authors.forename: Irfan
authors.initials: I
authors.lastname: Baig
authors.forename: Alfredo F
authors.initials: AF
authors.lastname: Braña
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rohr
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism; D003001:Cloning, Molecular; D003837:Deoxy Sugars / Q000096:biosynthesis; D006601:Hexoses / Q000096:biosynthesis; D008969:Molecular Sequence Data; D005810:Multigene Family; D009279:Naphthacenes / Q000378:metabolism; D013305:Streptomyces griseus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D003837:Deoxy Sugars; D006601:Hexoses; D009279:Naphthacenes; C407877:olivose; C020938:tetracenomycin C; C020615:digitoxose