Combinatorial biosynthesis of antitumor deoxysugar pathways in Streptomyces griseus: Reconstitution of "unnatural natural gene clusters" for the biosynthesis of four 2,6-D-dideoxyhexoses.
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.
Pérez
María
M
Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, Oviedo, Spain.
Lombó
Felipe
F
Baig
Irfan
I
Braña
Alfredo F
AF
Rohr
Jürgen
J
Salas
José A
JA
Méndez
Carmen
C
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*
D000970:Antineoplastic Agents; D003837:Deoxy Sugars; D006601:Hexoses; D009279:Naphthacenes; C407877:olivose; C020938:tetracenomycin C; C020615:digitoxose