Production of FK520 by Streptomyces tubercidicus.
The discovery of immunosuppressant compounds created the conditions for the successful transplantations. Effective immunosuppressant compounds were isolated from cultures of different microorganisms, among others macrolide type immunosuppressants, FK506 and FK520, were isolated from the fermentation broths of Streptomyces species. In this study a screening program was carried out to isolate microorganisms, which produce macrolide type immunosuppressant compounds. More than 40,000 actinomycete strains were investigated in the screening program comprising chemical, microbiological and PCR methods for the investigation of the cultures. Actinomycete strains with FK520 biosynthesizing ability were isolated in the program, which were identified as isolates of the Streptomyces tubercidicus species according to the taxonomical investigations. A part of the 31-O-demethyl-FK520 methyltransferase gene of the isolated S. tubercidicus was sequenced and it showed 88% homology to that of Streptomyces hygroscopicus. Till now strains of the Streptomyces hygroscopicus species were known to produce FK520 and this study proved that strains of other Streptomyces species have FK520 biosynthetic ability.
Kónya
Attila
A
IVAX Drug Research Institute Ltd., 1045 Budapest Berlini ùt 47-49, Hungary. h8773kon@ella.hu
Szabó
Zsuzsanna
Z
Láng
Ildikó
I
Barta
István
I
Salát
János
J
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D003470:Culture Media; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005285:Fermentation; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism*; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012988:Soil Microbiology; D013302:Streptomyces / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016559:Tacrolimus / Q000737:chemistry
D001426:Bacterial Proteins; D003470:Culture Media; D007166:Immunosuppressive Agents; D018942:Macrolides; D003577:Cytochrome P-450 Enzyme System; C101653:FK506 macrolide 9-hydroxylase, Streptomyces; D016559:Tacrolimus