ORF7 from Amycolatopsis orientalis catalyzes decarboxylation of N δ -methylarginine and amine oxidation of arginine: Biosynthetic implications
| Autor: | Natalie L. Kingston, Christopher T. Calderone, Yun Liu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Methylarginine Arginine biology Chemistry Decarboxylation Stereochemistry Biophysics biology.organism_classification Biochemistry Analytical Chemistry Amino acid 03 medical and health sciences chemistry.chemical_compound Polyketide 030104 developmental biology Biosynthesis Molecular Biology Amycolatopsis orientalis Oxidative decarboxylation |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1865:99-106 |
| ISSN: | 1570-9639 |
| Popis: | A key step in the biosynthesis of the polyene polyketide ECO-0501 by Amycolatopsis orientalis ATCC 43491 is thought to involve oxidative decarboxylation of arginine or Nδ-methylarginine to the corresponding primary amide. This reaction is the centerpiece of a recently identified biosynthetic cassette that generates 4-guanidinobutyryl thioesters to serve as starter units for polyketide synthesis. We examined the reaction of ORF7, the predicted ECO-0501 biosynthetic decarboxylase, with arginine, and saw no evidence of decarboxylation. Instead, we observed exclusive amine oxidation to generate 2-oxoarginine, with a kcat/KM,Arg of 5.6 × 106 M− 1 s− 1, typical of values measured for physiological amino acid decarboxylases. In contrast, when ORF7 was incubated with Nδ-methylarginine, we observed exclusive decarboxylation to generate 4-(N1-methylguanidino)butyramide. These differing reactive pathways provide insight into the biosyntheses of guanidinobutyryl-derived polyketides and demonstrate the biosynthetic versatility of arginine-processing decarboxylases. In addition, it suggests that ORF7 may be an incisive model system for dissecting the determinants of flavoprotein-catalyzed oxidase and monooxygenase modes of reactivity. |
| Databáze: | OpenAIRE |
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