The determinants of activity and specificity in actinorhodin type II polyketide ketoreductase
Javidpour, P; Bruegger, J; Srithahan, S; Korman, TP; Crump, MP; Crosby, J; Burkart, MD; Tsai, SC
| HERO ID | 2900229 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | The determinants of activity and specificity in actinorhodin type II polyketide ketoreductase |
| Authors | Javidpour, P; Bruegger, J; Srithahan, S; Korman, TP; Crump, MP; Crosby, J; Burkart, MD; Tsai, SC |
| Volume | 20 |
| Issue | 10 |
| Page Numbers | 1225-1234 |
| Abstract | In the actinorhodin type II polyketide synthase, the first polyketide modification is a regiospecific C9-carbonyl reduction, catalyzed by the ketoreductase (actKR). Our previous studies identified the actKR 94-PGG-96 motif as a determinant of stereospecificity. The molecular basis for reduction regiospecificity is, however, not well understood. In this study, we examined the activities of 20 actKR mutants through a combination of kinetic studies, PKS reconstitution, and structural analyses. Residues have been identified that are necessary for substrate interaction, and these observations have suggested a structural model for this reaction. Polyketides dock at the KR surface and are steered into the enzyme pocket where C7-C12 cyclization is mediated by the KR before C9-ketoreduction can occur. These molecular features can potentially serve as engineering targets for the biosynthesis of novel, reduced polyketides. |
| Doi | 10.1016/j.chembiol.2013.07.016 |
| Pmid | 24035284 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: Chemistry & biology ISSN: 1879-1301 |
| Is Public | Yes |
| Language Text | English |