Directed biosynthesis of fluorinated pseurotin A, synerazol and gliotoxin.
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.
Igarashi
Yasuhiro
Y
Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398, Japan. yas@pu-toyama.ac.jp
Yabuta
Yukihiro
Y
Sekine
Akira
A
Fujii
Kiyonaga
K
Harada
Ken-Ichi
K
Oikawa
Tsutomu
T
Sato
Mayumi
M
Furumai
Tamotsu
T
Oki
Toshikazu
T
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000935:Antifungal Agents / Q000096:biosynthesis* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000378:metabolism*; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D005285:Fermentation; D005459:Fluorides / Q000737:chemistry / Q000378:metabolism*; D005912:Gliotoxin / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D011760:Pyrrolidinones / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D011760:Pyrrolidinones; C068886:synerazol; C012013:pseurotin; D005912:Gliotoxin; D005459:Fluorides