Glycosylation of acyl carrier protein-bound polyketides during pactamycin biosynthesis
| Autor: | Mostafa E. Abugrain, Auday A. Eida, Corey J. Brumsted, Taifo Mahmud |
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| Rok vydání: | 2019 |
| Předmět: |
animal structures
Glycosylation Stereochemistry Decarboxylation Article 03 medical and health sciences Polyketide chemistry.chemical_compound Bacterial Proteins Biosynthesis Polyketide synthase Hydrolase Cloning Molecular Molecular Biology 030304 developmental biology 0303 health sciences biology Pactamycin 030302 biochemistry & molecular biology Gene Expression Regulation Bacterial Cell Biology Streptomyces Acyl carrier protein chemistry Polyketides biology.protein lipids (amino acids peptides and proteins) Carrier Proteins Polyketide Synthases Protein Binding |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| DOI: | 10.1038/s41589-019-0314-6 |
| Popis: | Glycosylation is a common modification reaction in natural products biosynthesis and has been known to be a post assembly line tailoring process in glycosylated polyketide biosynthesis. Here, we show that in pactamycin biosynthesis glycosylation can take place on an acyl carrier protein (ACP)-bound polyketide intermediate. Using in vivo gene inactivation, chemical complementation, and in vitro pathway reconstitution we demonstrate that the 3-aminoacetophenone moiety of pactamycin is derived from 3-aminobenzoic acid by a set of discrete polyketide synthase proteins via a 3-[3-aminophenyl]3-oxopropionyl-ACP intermediate. This ACP-bound intermediate is then glycosylated by an N-glycosyltransferase, PtmJ, providing a sugar precursor for the formation of the aminocyclopentitol core structure of pactamycin. This is the first example of glycosylation of a small molecule while tethered to a carrier protein. Additionally, we demonstrate that PtmO is a hydrolase that is responsible for the release of the ACP-bound product to a free β-ketoacid that subsequently undergoes decarboxylation. |
| Databáze: | OpenAIRE |
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