Rational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite
| Autor: | Thomas J. Simpson, Russell J. Cox, Ahmed A. Yakasai, Walid Bakeer, Colin M. Lazarus, Katja M. Fisch, Zahida Wasil, Zhongshu Song, Andy M. Bailey, Jennifer Pedrick |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular biology Pyridones Aspergillus oryzae Metabolite General Chemistry Computational biology biology.organism_classification Biochemistry Catalysis Domain (software engineering) Polyketide chemistry.chemical_compound Colloid and Surface Chemistry chemistry Biosynthesis Gene cluster Secondary metabolism Oxidation-Reduction Polyketide Synthases Gene |
| Zdroj: | Journal of the American Chemical Society. 133:16635-16641 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja206914q |
| Popis: | The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism. We conducted rational domain swaps between the polyketide synthases encoding the biosynthesis of the closely related compounds tenellin and desmethylbassianin. Expression of the hybrid synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin. |
| Databáze: | OpenAIRE |
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