BIOL 120 |
| The antibacterial activity of erythromycin, an important polyketide natural product, requires the transfer of two unusual glycosyl groups, mycarose and desosamine, onto the macrocyclic aglycone. The biosynthetic pathways of both sugars were reconstituted in recombinant strain of E.coli to yield bioactive 6-deoxyerythromycin D from propionate, thereby yielding a fundamentally new activity-based screening assay for enhancing the efficiency of biosynthetic engineering of macrolide antibiotics. After three rounds of screening, 6-deoxyerythromycin D overproducers were identified with significant phenotypic modifications in the mycarose biosynthetic pathway. The same screening system was also used to evolve improved catalysts for precursor directed biosynthesis. These results represent the first example of directed evolution of an antibiotic pathway in E. coli, and open the door for harnessing the power of genetics for mechanistic investigations into polyketide synthases and for biosynthetic engineering.
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Poster Session
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |
