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Lett Appl Microbiol. 2011 Feb;52(2):129-37. doi: 10.1111/j.1472-765X.2010.02973.x. Epub 2010 Dec 22.

Knocking out of tailoring genes eryK and eryG in an industrial erythromycin-producing strain of Saccharopolyspora erythraea leading to overproduction of erythromycin B, C and D at different conversion ratios.

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1
East China University of Science and Technology, Shanghai, China.

Abstract

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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