Synergistic Actions of Tailoring Enzymes in Pradimicin Biosynthesis
| Autor: | Jon Y. Takemoto, Shuwei Zhang, Thomas Anderson, Kandy Napan, Jixun Zhan, Whitney Morgan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
biology Stereochemistry Organic Chemistry Streptomyces coelicolor Molecular Conformation Cytochrome P450 biology.organism_classification Biochemistry Biosynthetic enzyme Article Amino acid chemistry.chemical_compound Enzyme chemistry Biosynthesis Cytochrome P-450 Enzyme System Combinatorial biosynthesis biology.protein Molecular Medicine Substrate specificity Anthracyclines Molecular Biology |
| Popis: | Three key tailoring enzymes in pradimicin biosynthesis: PdmJ, PdmW, and PdmN, were investigated. PdmW was characterized as the C-6 hydroxylase by structural characterization of the corresponding product, 6-hydroxy-G-2A. The efficiencies of the C-5 and C-6 hydroxylations, catalyzed respectively by PdmJ and PdmW, were low when they were expressed individually with the early biosynthetic enzymes that form G-2A. When these two cytochrome P450 enzymes were co-expressed, a dihydroxylated product, 5,6-dihydroxy-G-2A, was efficiently produced, indicating that these two enzymes work synergistically in pradimicin biosynthesis. Heterologously expressed PdmN in Streptomyces coelicolor CH999 converted G-2A to JX137a by ligating a unit of D-alanine to the carboxyl group. PdmN has relaxed substrate specificity toward both amino acid donors and acceptors. Through combinatorial biosynthesis, a series of new pradimicin analogues were produced. |
| Databáze: | OpenAIRE |
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