title: Enhancement of doxorubicin production by expression of structural sugar biosynthesis and glycosyltransferase genes in Streptomyces peucetius.
abstract: To enhance doxorubicin (DXR) production, the structural sugar biosynthesis genes desIII and desIV from Streptomyces venezuelae ATCC 15439 and the glycosyltransferase pair dnrS/dnrQ from Streptomyces peucetius ATCC 27952 were cloned into the expression vector pIBR25, which contains a strong ermE promoter. The recombinant plasmids pDnrS25 and pDnrQS25 were constructed for overexpression of dnrS and the dnrS/dnrQ pair, whereas pDesSD25 and pDesQS25 were constructed to express desIII/desIV and dnrS/dnrQ-desIII/desIV, respectively. All of these recombinant plasmids were introduced into S. peucetius ATCC 27952. The recombinant strains produced more DXR than the S. peucetius parental strain: a 1.2-fold increase with pDnrS25, a 2.8-fold increase with pDnrQS25, a 2.6-fold increase with pDesSD25, and a 5.6-fold increase with pDesQS25. This study showed that DXR production was significantly enhanced by overexpression of potential biosynthetic sugar genes and glycosyltransferase.
authors.affiliation: Institute of Biomolecule Reconstruction (iBR), Department of Pharmaceutical Engineering, Sun Moon University, #100 Kalsan-ri, Tangjeong-myeon, Asansi, Chungnam 336-708, Republic of Korea.
authors.forename: Sailesh
authors.initials: S
authors.lastname: Malla
authors.forename: Narayan Prasad
authors.initials: NP
authors.lastname: Niraula
authors.forename: Kwangkyoung
authors.initials: K
authors.lastname: Liou
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System; D003837:Deoxy Sugars / Q000235:genetics / Q000378:metabolism*; D004317:Doxorubicin / Q000096:biosynthesis*; D015870:Gene Expression; D016695:Glycosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D003837:Deoxy Sugars; C096749:DnrQ protein, Streptomyces peucetius; D004317:Doxorubicin; D003577:Cytochrome P-450 Enzyme System; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; D016695:Glycosyltransferases; C096750:DnrS protein, Streptomyces peucetius