Abstract
The biosynthesis of the azabicyclic ring system of the azinomycin family of antitumor agents represents the "crown jewel" of the pathway and is a complex process involving at least 14 enzymatic steps. This study reports on the first biosynthetic step, the inroads, in the construction of the novel aziridino [1,2-a]pyrrolidine, azabicyclic core, allowing us to support a new mechanism for azabicycle formation.
MeSH terms
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Acetyl Coenzyme A / metabolism
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Acetylation
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Aldehyde Oxidoreductases / genetics
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Aldehyde Oxidoreductases / metabolism*
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Amino-Acid N-Acetyltransferase / genetics
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Amino-Acid N-Acetyltransferase / metabolism*
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Antibiotics, Antineoplastic / chemistry
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Antibiotics, Antineoplastic / metabolism
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Antibiotics, Antineoplastic / pharmacology
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Antineoplastic Agents, Alkylating / chemistry
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Antineoplastic Agents, Alkylating / metabolism*
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Antineoplastic Agents, Alkylating / pharmacology
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Azabicyclo Compounds / chemistry
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Azabicyclo Compounds / metabolism*
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Azabicyclo Compounds / pharmacology
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Biocatalysis
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Dipeptides / chemistry
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Dipeptides / metabolism
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Dipeptides / pharmacology
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Drug Design*
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Gene Knockout Techniques
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Glutamic Acid / metabolism
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Intercellular Signaling Peptides and Proteins
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Molecular Structure
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Mutation
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Naphthalenes / chemistry
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Naphthalenes / metabolism
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Naphthalenes / pharmacology
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Peptides / chemistry
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Peptides / metabolism
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Peptides / pharmacology
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Phosphotransferases (Carboxyl Group Acceptor) / genetics
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Phosphotransferases (Carboxyl Group Acceptor) / metabolism*
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Pyrrolidines / chemistry
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Pyrrolidines / metabolism*
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Pyrrolidines / pharmacology
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Recombinant Proteins / metabolism
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Streptomyces / enzymology
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Streptomyces / metabolism
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Substrate Specificity
Substances
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Antibiotics, Antineoplastic
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Antineoplastic Agents, Alkylating
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Azabicyclo Compounds
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Bacterial Proteins
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Dipeptides
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Intercellular Signaling Peptides and Proteins
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Naphthalenes
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Peptides
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Pyrrolidines
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Recombinant Proteins
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azinomycin B
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azinomycin A
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Glutamic Acid
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Acetyl Coenzyme A
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Aldehyde Oxidoreductases
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N-acetyl-gamma-glutamyl-phosphate reductase
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Amino-Acid N-Acetyltransferase
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Phosphotransferases (Carboxyl Group Acceptor)
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acetylglutamate kinase