Abstract:Monensin is a kind of polyether antibiotic produced by Streptomyces cinnamonensis (S. cinnamonensis), which is widely used in fields such as agriculture and animal husbandry with the advantages of low tendency to resistance and environmentally friendly properties. The author systematically investigated the fermentation performance improvement of S. cinnamonensis srain 2110 by combination of space mutation and genetic engineering breeding. High-yielding mutants from space mutation were selected through resistance screening combined with a microplate culture system. Results showed that a highly monensin producing mutant S. cinnamonensis G43 (G43) was obtained with a relatively good genetic stability, in which its monensin titer increased by 16.5% as compared to the parental strain. Subsequently, independent and tandem overexpression of monensin synthesis regulatory genes were conducted around the mutant strain. With successful integration of regulatory genes monRI and dasR, the engineering strain G43-dasR-monRI was finally obtained, and its monensin titer reached 11.3 kU/mL in a 5 L bio-fermenter, representing a 33.1% increase compared to the parental strain 2110. The results demonstrated that the combination of space mutation and genetic engineering breeding can be effectively applied to select high-yield strains for monensin production and may provide a reference for strain improvement of other polyether antibiotic-producing microorganisms.
