Enzymatic Synthesis of Molecular Skeletons of Complex Antitumor Antibiotics with Non-ribosomal Peptide Synthetases
スポンサーリンク
概要
- 論文の詳細を見る
Nonribosomal peptide synthetase (NRPS) is a programmable modular machinery which produces a number of biologically active small–molecule peptides. Recent progress on understanding the catalytic mechanism of NRPS enabled us to engineer this complex catalytic system. We demonstrated both in vivo and in vitro enzymatic synthesis of complex natural antitumor peptides echinomycin and saframycin. An Escherichia coli–based expression system served as a flexible yet robust platform for producing complex natural products and their analogs by deletion, mutation and swapping of a specific subunit. The excised thioesterase domain of echinomycin exhibited remarkable substrate tolerance and created a cyclic peptide library. On the other hand, saframycin NRPS catalyzed highly unusual seven–step transformations to construct a pentacyclic tetrahydro–isoquinoline skeleton.
- 社団法人 有機合成化学協会の論文
- 2009-11-01
著者
-
Oikawa Hideaki
Div. Of Chemistry Graduate School Of Sci. Hokkaido Univ.
-
Oikawa Hideaki
Division Of Applied Bioscience Graduate School Of Agriculture Hokkaido University
-
WATANABE Kenji
University of Shizuoka, School of Pharmaceutical Sciences
-
OGURI Hiroki
Division of Chemistry, Graduate School of Science, Hokkaido University
-
Oguri Hiroki
Division Of Chemistry Graduate School Of Science Hokkaido University
-
Watanabe Kenji
Division Of Chemistry Graduate School Of Science Hokkaido University
-
Watanabe Kenji
University Of Hyogo
-
Watanabe Kenji
School Of Pharmaceutical Sciences University Of Shizuoka
関連論文
- Reconstruction of the saframycin core scaffold defines dual Pictet-Spengler mechanisms
- Bioorganic Studies Utilizing Rationally Designed Synthetic Molecules : Absolute Configuration of Ciguatoxin and Development of Immunoassay Systems
- Cloning of a Gene Cluster Responsible for the Biosynthesis of Diterpene Aphidicolin, a Specific Inhibitor of DNA Polymerase α
- Diterpene Cyclases Responsible for the Biosynthesis of Phytoalexins, Momilactones A, B, and Oryzalexins A-F in Rice
- Potent Inhibition of Macrophomate Synthase by Reaction Intermediate Analogs
- Characterization of a Rice Gene Family Encoding Type-A Diterpene Cyclases
- NMR Determination of the Absolute Configuration of a Macrophomate Synthase Inhibitor by Using an Axial Chiral Reagent(Organic Chemistry)
- Total Synthesis of (±) -syn-Copalol(Organic Chemistry)
- Total Synthesis of (+)-Albicanol and (+)-Albicanyl Acetate
- Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics
- Identification of Diterpene. Biosynthetic Gene Clusters and Functional Analysis of Labdane-Related Diterpene Cyclases in Phomopsis amygdali
- Purification and N-Terminal Amino Acid Sequence of Solanapyrone Synthase, A Natural Diels-Alderase from Alternaria solani
- Identification of a Gene Cluster of Polyether Antibiotic Lasalocid from Streptomyces lasaliensis
- Enzymatic Synthesis of Molecular Skeletons of Complex Antitumor Antibiotics with Non-ribosomal Peptide Synthetases
- Relative and Absolute Configuration of Antitumor Agent SW-163D
- P-556 Biosynthetic Study of Polyether Antibiotic Lasalocid
- P-528 Biosynthetic Study of Antitumor Antibiotic Echinomycin : Formation of Quinoxaline Ring and Enzymatic Macrocyclization
- Involvement of the Diels-Alderases in the Biosynthesis of Natural Products
- Total Biosynthesis of Diterpene Aphidicolin, a Specific Inhibitor of DNA Polymerase α: Heterologous Expression of Four Biosynthetic Genes in Aspergillus oryzae
- Studies on the Later Stage of the Biosynthesis of Pleuromutilin
- The Relative and Absolute Configuration of PF1140
- Biosynthetic Study of FR-900848: Origin of the Aminodeoxynucleoside Part
- P-264 BIOSYNTHETIC STUDY OF FR-900848
- Total Biosynthesis of Diterpene Aphidicolin, a Specific Inhibitor of DNA Polymerase α : Heterologous Expression of Four Biosynthetic Genes in Aspergillus oryzae
- IS A SPINAL CORD REQUIRED FOR XENOPUS TAIL REGENERATION?(Developmental Biology,Abstracts of papers presented at the 75^ Annual Meeting of the Zoological Society of Japan)
- Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics