The dynamic structure of jadomycin B and the amino acid incorporation step of its biosynthesis.
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.
Rix
Uwe
U
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 907 Rose Street, Lexington, Kentucky 40536-0082, USA.
Zheng
Jianting
J
Remsing Rix
Lily L
LL
Greenwell
Lisa
L
Yang
Keqian
K
Rohr
Jürgen
J
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D007532:Isoleucine / Q000737:chemistry / Q000378:metabolism; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
D000596:Amino Acids; D007546:Isoquinolines; D007532:Isoleucine; C081750:jadomycin B