Priming of Azabicycle Biosynthesis in the Azinomycin Class of Antitumor Agents

Biochemistry. 2017 Feb 14;56(6):805-808. doi: 10.1021/acs.biochem.6b01108. Epub 2017 Feb 6.

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

  • Acetyl Coenzyme A / metabolism
  • Acetylation
  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / metabolism*
  • Amino-Acid N-Acetyltransferase / genetics
  • Amino-Acid N-Acetyltransferase / metabolism*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / metabolism*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Azabicyclo Compounds / chemistry
  • Azabicyclo Compounds / metabolism*
  • Azabicyclo Compounds / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biocatalysis
  • Dipeptides / chemistry
  • Dipeptides / metabolism
  • Dipeptides / pharmacology
  • Drug Design*
  • Gene Knockout Techniques
  • Glutamic Acid / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Molecular Structure
  • Mutation
  • Naphthalenes / chemistry
  • Naphthalenes / metabolism
  • Naphthalenes / pharmacology
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology
  • Phosphotransferases (Carboxyl Group Acceptor) / genetics
  • Phosphotransferases (Carboxyl Group Acceptor) / metabolism*
  • Pyrrolidines / chemistry
  • Pyrrolidines / metabolism*
  • Pyrrolidines / pharmacology
  • Recombinant Proteins / metabolism
  • Streptomyces / enzymology
  • Streptomyces / metabolism
  • Substrate Specificity

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Azabicyclo Compounds
  • Bacterial Proteins
  • Dipeptides
  • Intercellular Signaling Peptides and Proteins
  • Naphthalenes
  • Peptides
  • Pyrrolidines
  • Recombinant Proteins
  • azinomycin B
  • azinomycin A
  • Glutamic Acid
  • Acetyl Coenzyme A
  • Aldehyde Oxidoreductases
  • N-acetyl-gamma-glutamyl-phosphate reductase
  • Amino-Acid N-Acetyltransferase
  • Phosphotransferases (Carboxyl Group Acceptor)
  • acetylglutamate kinase