Knocking out of tailoring geneseryKanderyGin an industrial erythromycin-producing strain ofSaccharopolyspora erythraealeading to overproduction of erythromycin B, C and D at different conversion ratios

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Aims:To overproduce erythromycin C, B or D and evaluate the effect of disruption of tailoring genes eryK and eryG in an industrial erythromycin producer.Methods and Results:The tailoring genes eryG and eryK were inactivated individually or simultaneously by targeted gene disruption in an industrial strain Saccharopolyspora erythraea HL3168 E3, resulting in the overproduction of erythromycin C (2·48 g l−1), B (1·70 g l−1) or D (2·15 g l−1) in the mutant strain QL-G, QL-K or QL-KG, respectively. Analysis of the erythromycin congeners throughout the fermentation indicated that, at the end of fermentation, comparatively large amount of erythromycin D (0·67 g l−1) was accumulated in QL-G, whereas only small amount of erythromycin D (0·10 g l−1) was produced in QL-K.Conclusions:Inactivation of tailoring genes eryG and eryK in the high producer did not affect the biosynthesis of erythromycin. However, erythromycin D could be more efficiently methylated by EryG than be hydroxylated by EryK.Significance and Impact of the Study:Development of the mutant strains provides a method for the economical large-scale production of potent lead compounds. The information about the accumulation and conversion of erythromycins in the industrial strains may contribute to further improving erythromycin production.

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