A genetically engineered strain of Saccharopolyspora erythraea that produces 6,12-dideoxyerythromycin A as the major fermentation product.
The erythromycin producer, Saccharopolyspora erythraea ER720, was genetically engineered to produce 6,12-dideoxyerythromycin A, a novel erythromycin derivative, as the major macrolide in the fermentation broth. Inspection of the biosynthetic pathway for erythromycin would suggest that production of this compound could be achieved simply through the disruption of two genes, that encoding the erythromycin C-6 hydroxylase (eryF) and that encoding the erythromycin C-12 hydroxylase (eryK). The double mutant, however, was found to produce a mixture of 6,12-dideoxyerythromycin A and the precursor, 6-deoxyerythromycin D. Complete conversion to the desired product (to the limit of detection by TLC) was achieved by inserting an additional copy of the eryG gene, encoding the erythromycin 3"-O-methyltransferase and driven by the ermE* promoter, into the S. erythraea chromosome.
Stassi
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Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, 1401 Sheridan Road, North Chicago, IL 60064, USA. diane.stassi@abbott.com
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Satter
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Jackson
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Maine
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D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry; D005285:Fermentation / Q000502:physiology; D005818:Genetic Engineering; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D016930:Saccharopolyspora / Q000235:genetics* / Q000378:metabolism*
C113836:6,12-dideoxyerythromycin A; D001426:Bacterial Proteins; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C078882:EryK protein, Saccharopolyspora erythraea; D008780:Methyltransferases