Biotechnological doxorubicin production: pathway and regulation engineering of strains for enhanced production.
Doxorubicin (DXR) is an anthracycline-type polyketide, typically produced by Streptomyces peucetius ATCC 27952. Like the biosynthesis of other secondary metabolites in Streptomyces species, DXR biosynthesis is tightly regulated, and a very low level of DXR production is maintained in the wild-type strain. Despite that DXR is one of the most broadly used and clinically important anticancer drugs, a traditional strain improvement strategy has long been practiced via recursive random mutagenesis, with little understanding of the molecular genetic basis underlying such enhanced DXR production. Since DXR titer enhancement is imperative in the fermentation industry, attaining a comprehensive understanding and its application of the specific regulatory systems that govern secondary metabolite production is an important aspect of metabolic engineering that can efficiently improve fermentation titers. In this mini-review, various efforts to improve the titers of DXR have been summarized based on biosynthetic and regulatory studies including transcriptional and product analyses.
Niraula
Narayan Prasad
NP
Institute of Biomolecule Reconstruction (iBR), Department of Pharmaceutical Engineering, Sun Moon University, Asansi, Chungnam 336-708, South Korea.
Kim
Seon-Hye
SH
Sohng
Jae Kyung
JK
Kim
Eung-Soo
ES
D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D004317:Doxorubicin / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering; D007218:Industrial Microbiology; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin