Guanidyl modification of the 1-azabicyclo[3.1.0]hexane ring in ficellomycin essential for its biological activity
| Autor: | Sumire Kurosawa, Kenichi Matsuda, Fumihito Hasebe, Makoto Nishiyama, Tomohisa Kuzuyama, Taro Shiraishi, Kazuo Shin-ya |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
DNA ligase Dipeptide Stereochemistry Organic Chemistry Ring (chemistry) Biochemistry Amino acid Hexane Structure-Activity Relationship chemistry.chemical_compound DNA Alkylation chemistry Biosynthesis Hexanes Intercellular Signaling Peptides and Proteins Moiety Physical and Theoretical Chemistry Azabicyclo Compounds Guanidine |
| Zdroj: | Organic & Biomolecular Chemistry. 18:5137-5144 |
| ISSN: | 1477-0539 1477-0520 |
| Popis: | The 1-azabicyclo[3.1.0]hexane ring is a key moiety in natural products for biological activities against bacteria, fungi, and tumor through DNA alkylation. Ficellomycin is a dipeptide that consists of l-valine and a non-proteinogenic amino acid with the 1-azabicyclo[3.1.0]hexane ring structure. Although the biosynthetic gene cluster of ficellomycin has been identified, the biosynthetic pathway currently remains unclear. We herein report the final stage of ficellomycin biosynthesis involving ring modifications and successive dipeptide formation. After the ring is formed, the hydroxy group of the ring is converted into the guanidyl unit by three enzymes, which include an aminotransferase with a novel inter ω-ω amino-transferring activity. In the last step, the resulting 1-azabicyclo[3.1.0]hexane ring-containing amino acid is connected with l-valine by an amino acid ligase to yield ficellomycin. The present study revealed a new machinery that expands the structural and biological diversities of natural products. |
| Databáze: | OpenAIRE |
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