Study on secondary metabolites of genetically engineered bacterium Streptomyces bingchengensis BCJ60
Polyketide compounds are a type of natural product produced by continuous condensation reactions of lower carboxylic acids catalyzed by polyketide synthase, including macrolides, tetracyclines, anthraquinones, and polyethers. From a pharmacological perspective, polyketide compounds are an important source of novel drugs, mainly used as antibiotics, immunosuppressants, antiparasitic agents, cholesterol lowering agents, and anti-tumor drugs. The function of each domain of polyketide synthase corresponds to the structure of the final product. Therefore, this correspondence can be used to edit biosynthetic genes and design synthetic products, thus creating a new research field – combinatorial biology of polyketide synthase. Scholars mainly generate new products by reducing, increasing, or replacing the modules and structural domains of polyketide synthase, such as by modifying the polyketide synthase gene cluster aveLAT-ACP in Streptomyces avermitilis to obtain a genetically engineered strain. Two new avermectin derivatives, 25 methyl ivermectin and 25 ethyl ivermectin, were isolated from the secondary metabolites of the strain.

In the previous research, our research group modified the milF gene encoding polyketide synthase in Streptomyces bingchengensis BC-120-4 to obtain the genetically engineered strain Streptomyces bingchengensis BCJ60. This strain cannot encode C-5 ketoreductase, thus blocking the synthesis of milbeimycin A3/A4/B2/B3. Through targeted genetic modification, the biosynthetic gene cluster may undergo changes, which may activate certain biosynthetic pathways to obtain new metabolites. Therefore, this study mainly focuses on the secondary metabolites of the genetically engineered strain Streptomyces bingchengensis BCJ60, in order to obtain highly effective insecticidal antibiotics with practical value.

 

 

This article systematically studied the secondary metabolites of the genetically engineered bacterium Streptomyces bingchengensis BCJ60, and obtained 11 compounds, among which compounds 1 and 2 are two new compounds. In previous studies, our research group has conducted preliminary research on the secondary metabolites of the genetically engineered bacterium Streptomyces bingchengensis BCJ60 and obtained 12 new compounds, all of which are milberellins. This indicates that through gene targeted modification, the biosynthetic gene cluster undergoes changes, activating certain biosynthetic pathways and obtaining new metabolites, which helps to further understand the biosynthetic mechanism of Mirella compounds. The insecticidal activity experiment of the new compound showed that compounds 1 and 2 exhibited significant killing activity against cinnabar mites and pine wood nematodes, and there was no significant difference compared to the commercial Mirbeimycin A3/A4. This indicates that compounds 1 and 2 are not only expected to serve as alternative insecticides to Mirbeimycin A3/A4, but also have the potential to obtain a new generation of agricultural or veterinary antibiotics with higher activity through structural modification.