Directed biosynthesis of fluorinated pseurotin A, synerazol and gliotoxin.

Abstract

Aspergillus fumigatus TP-F0196 produces pseurotin A, synerazol and gliotoxin. Phenylalanine is a common biosynthetic precursor of these antibiotics. Feeding fluorophenylalanine to the culture induced the production of novel fluorinated analogs. These fluorinated antibiotics were obtained from the culture broth by solvent extraction and purified by chromatographies, and their antimicrobial and antitumor activities were investigated. Among the novel fluorinated analogs, 19- and 20-fluorosynerazols exhibited potent anti-angiogenic activity in the chorioallantoic membrane assay. In addition, 19-fluorosynerazol showed more potent cytocidal activity against several cancer cell lines than synerazol.

• Authors: Yasuhiro Igarashi, Yukihiro Yabuta, Akira Sekine, Kiyonaga Fujii, Ken-Ichi Harada, Tsutomu Oikawa, Mayumi Sato, Tamotsu Furumai, Toshikazu Oki
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 57 Issue 11 Pg. 748-54 (Nov 2004) ISSN: 0021-8820 [Print] England
• PMID: 15712670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antifungal Agents
• Immunosuppressive Agents
• Pyrrolidinones
• synerazol
• pseurotin
• Gliotoxin
• Fluorides

Topics

• Angiogenesis Inhibitors (pharmacology)
• Antifungal Agents (biosynthesis, pharmacology)
• Aspergillus fumigatus (metabolism)
• Bacteria (drug effects)
• Cell Line, Tumor
• Chromatography, High Pressure Liquid
• Drug Screening Assays, Antitumor
• Fermentation
• Fluorides (chemistry, metabolism)
• Gliotoxin (biosynthesis, pharmacology)
• Humans
• Immunosuppressive Agents (metabolism, pharmacology)
• Magnetic Resonance Spectroscopy
• Mass Spectrometry
• Microbial Sensitivity Tests
• Pyrrolidinones (pharmacology)