Enhancement of doxorubicin production by expression of structural sugar biosynthesis and glycosyltransferase genes in Streptomyces peucetius.
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.
Malla
Sailesh
S
Institute of Biomolecule Reconstruction (iBR), Department of Pharmaceutical Engineering, Sun Moon University, #100 Kalsan-ri, Tangjeong-myeon, Asansi, Chungnam 336-708, Republic of Korea.
Niraula
Narayan Prasad
NP
Liou
Kwangkyoung
K
Sohng
Jae Kyung
JK
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
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