The Dynamic Structure of Jadomycin B and the Amino Acid Incorporation Step of Its Biosynthesis

• Published in: Journal of the American Chemical Society 2004-04, Vol.126 (14), p.4496-4497
• Main Authors: Rix, Uwe, Zheng, Jianting, Remsing Rix, Lily L, Greenwell, Lisa, Yang, Keqian, Rohr, Jürgen
• Format: Article
• Language: English
• Subjects: Amino Acids - chemistry; Amino Acids - metabolism; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Hydrogen Bonding; Isoleucine - chemistry; Isoleucine - metabolism; Isoquinolines - chemistry; Isoquinolines - metabolism; Medical sciences; Models, Molecular; Molecular Conformation; Nuclear Magnetic Resonance, Biomolecular; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja031724o

Jadomycin B, an antifungal antibiotic with a unique 8H-benz[b]oxazolo[3,2-f]phenanthridine pentacyclic skeleton produced by the bacterium Streptomyces venezuelae ISP 5230, exists in a dynamic equilibrium of two diastereomers differing in the configuration of C-3a. Several novel jadomycins with various amino acid-derived 1-side chains could be generated, by replacing isoleucine in the production medium of S. venezuelae with other amino acids. These two findings led to the conclusion that a nonenzymatic reaction with the amino acid followed by a likewise nonenzymatic cyclization cascade are crucial for its late biosynthesis.