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.
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.
Authors: Benjamin Kirm; Vasilka Magdevska; Miha Tome; Marinka Horvat; Katarina Karničar; Marko Petek; Robert Vidmar; Spela Baebler; Polona Jamnik; Štefan Fujs; Jaka Horvat; Marko Fonovič; Boris Turk; Kristina Gruden; Hrvoje Petković; Gregor Kosec Journal: Microb Cell Fact Date: 2013-12-17 Impact factor: 5.328