Discovery of a Phosphonoacetic Acid Derived Natural Product by Pathway Refactoring
| Autor: | Bin Wang, Kou San Ju, Huimin Zhao, Todd S. Freestone |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Phosphonoacetic Acid Hydrolases Phosphorous Acids Biomedical Engineering computer.software_genre Biochemistry Genetics and Molecular Biology (miscellaneous) Streptomyces 03 medical and health sciences chemistry.chemical_compound Synthetic biology Gene Genetics Biological Products Natural product biology Strain (biology) General Medicine biology.organism_classification Chemical space 030104 developmental biology chemistry Code refactoring Multigene Family Synthetic Biology computer |
| Zdroj: | ACS synthetic biology. 6(2) |
| ISSN: | 2161-5063 |
| Popis: | The activation of silent natural product gene clusters is a synthetic biology problem of great interest. As the rate at which gene clusters are identified outpaces the discovery rate of new molecules, this unknown chemical space is rapidly growing, as too are the rewards for developing technologies to exploit it. One class of natural products that has been underrepresented is phosphonic acids, which have important medical and agricultural uses. Hundreds of phosphonic acid biosynthetic gene clusters have been identified encoding for unknown molecules. Although methods exist to elicit secondary metabolite gene clusters in native hosts, they require the strain to be amenable to genetic manipulation. One method to circumvent this is pathway refactoring, which we implemented in an effort to discover new phosphonic acids from a gene cluster from Streptomyces sp. strain NRRL F-525. By reengineering this cluster for expression in the production host Streptomyces lividans, utility of refactoring is demonstrated with the isolation of a novel phosphonic acid, O-phosphonoacetic acid serine, and the characterization of its biosynthesis. In addition, a new biosynthetic branch point is identified with a phosphonoacetaldehyde dehydrogenase, which was used to identify additional phosphonic acid gene clusters that share phosphonoacetic acid as an intermediate. |
| Databáze: | OpenAIRE |
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