With the development of molecular biology in the past decade, especially on the basis of the cloning of antibiotic biosynthetic gene clusters and the elucidation of antibiotic biosynthetic pathways, metabolic engineering technology has been proposed and gradually developed to meet the needs of innovative microbial drug research. Currently, in a reasonable, directed and efficient pathway for improving antibiotic strain, principles and techniques of molecular genetics are used to specifically and appropriately modify the synthetic route of natural products in the “Cell Factory” to obtain recombinant strains, thus increasing production or optimize the components of fermentation. The key to the successful use of metabolic engineering is to recognize and understand the biosynthesis and regulatory mechanisms of complex antibiotics at gene and protein function level, which is the molecular and biochemical basis for the genetic manipulation of metabolic pathways in microorganisms. However, due to the lack of understanding of the biosynthesis mechanism of lincomycin, the application of this technology to improve industrial production strains of lincomycin is greatly limited.
Lincomycin and its chemically semi-synthesized downstream product, clindamycin, are widely used clinically for many years. Currently, lincomycin is mainly produced by fermentation of Streptomyces lincolnensis. Although Lincomycin has been used clinically for several decades, there are few studies on its biosynthetic pathway.
Chemical syntheses of structural analogues or derivatives of lincomycin have been continuously studied in the art. However, lincosamide antibiotics that have been clinically used so far only include lincomycin and clindamycin which is chemically semi-synthesized based on lincomycin. Production of intermediates or structural analogues of lincomycin biosynthesis by genetically engineered lincomycin-producing bacteria will be conducive to elucidate the biosynthesis pathways of lincomycin, thereby producing new lincosamide antibiotics using combinatorial bio-synthesis method based on the results of biosynthetic mechanism studies.