Heterologous expression of a model polyketide pathway in doxorubicin-overproducing Streptomyces industrial mutants

The Streptomyces peucetius OIM (Overproducing Industrial Mutant) strain is a recursively-mutated and optimally-screened strain used for the industrial production of polyketide antibiotics, such as doxorubicin (DXR). Using the S. peucetius OIM mutant strain as a surrogate host, a model minimal polyketide pathway for aloesaponarin II, an actinorhodin shunt product, was cloned in a high-copy conjugative plasmid, followed by functional pathway expression and quantitative metabolite analysis. The level of aloesaponarin II production was noted as being significantly higher in the OIM strain than in the wild-type S. peucetius, as well as in the regulatory network-stimulated S. coelicolor mutant strain. Moreover, the aloesaponarin II production level was seen to be even higher in a down-regulator wblA_spe-deleted S. peucetius OIM strain, implying that the rationally-engineered S. peucetius OIM mutant strain could be used as an efficient surrogate host for the high expression of foreign polyketide pathways.