Recognition of extended linear and cyclised polyketide mimics by a Type II acyl carrier protein
| Autor: | John Crosby, Christopher D. Bailey, Christopher Williams, Thomas J. Simpson, Christine L. Willis, Matthew P. Crump, Xu Dong |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification biology 010405 organic chemistry Stereochemistry Streptomyces coelicolor Fatty acid Substrate (chemistry) Small acidic protein General Chemistry biology.organism_classification 01 natural sciences Actinorhodin 0104 chemical sciences 03 medical and health sciences Polyketide chemistry.chemical_compound Acyl carrier protein 030104 developmental biology Biosynthesis chemistry biology.protein |
| Zdroj: | Dong, X, Bailey, C, Williams, C, Crosby, J, Simpson, T, Willis, C & Crump, M 2016, ' Recognition of extended linear and cyclised polyketide mimics by a Type II acyl carrier protein ', Chemical Science, vol. 7, no. 3, pp. 1779-1785 . https://doi.org/10.1039/C5SC03864B |
| DOI: | 10.1039/C5SC03864B |
| Popis: | Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP's capacity to sequester a non-polar versus a phenolic aromatic ring (that more closely mimics a polyketide intermediate) as well as investigations with extended polyketide chain surrogates. The binding of these mimics has been assessed using high-resolution solution NMR studies and high-resolution structure determination. These results reveal that surprisingly a PKS ACP is able to bind and sequester a bulky non-polar substrate containing an aromatic ring in a fatty acid type binding mode, but the introduction of even a small degree of polarity favours a markedly different association at a surface site that is distinct from that employed by fatty acid ACPs. |
| Databáze: | OpenAIRE |
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