Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis† †Electronic supplementary information (ESI) available: Experimental procedures and additional tables, figures, chromatograms and results from biological assays. See DOI: 10.1039/c6sc02803a Click here for additional data file
| Autor: | Awodi, U. R., Ronan, J. L., Masschelein, J., de los Santos, E. L. C., Challis, G. L. |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6539 2041-6520 |
| Popis: | Polyketide synthase reductive chain release and subsequent transamination are key steps in the biosynthesis of polyketide alkaloids in actinobacteria. Actinobacteria produce a variety of polyketide alkaloids with unusual structures. Recently, it was shown that a type I modular polyketide synthase (PKS) is involved in the assembly of coelimycin P1, a polyketide alkaloid produced by Streptomyces coelicolor M145. However, the mechanisms for converting the product of the PKS to coelimycin P1 remain to be elucidated. Here we show that the C-terminal thioester reductase (TR) domain of the PKS and an ω-transaminase are responsible for release of the polyketide chain as an aldehyde and its subsequent reductive amination. Bioinformatics analyses identified numerous gene clusters in actinobacterial genomes that encode modular PKSs with a C-terminal TR domain and a homolog of the ω-transaminase. These are predicted to direct the biosynthesis of both known and novel polyketide alkaloids, suggesting that reductive chain release and transamination constitutes a conserved mechanism for the biosynthesis of such metabolites. |
| Databáze: | OpenAIRE |
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