Genetic relationships among actinomycetes that produce the immunosuppressant macrolides FK506, FK520/FK523 and rapamycin.
A polyphasic taxonomic study was undertaken to establish the genetic and phenotypic relationships among six actinomycetes that produce the immunosuppressant macrolides FK506, FK520/FK523 and rapamycin. Chemotaxonomic studies reveal that all have Type I cell walls. Gas chromatography (GC) of fatty acid methyl esters revealed patterns consistent for strains of Streptomyces with 16:0 and 15:0 anteiso predominating. Principal component analysis of GC data revealed distinct profiles for each culture. Reciprocal DNA homology studies at Tm-25 showed the rapamycin-producing strain and one FK506-producing strain to have 38-50% homology with the type strain of Streptomyces hygroscopicus (ATCC 27438). The remaining strains exhibited 6-17% homology. To further explore the relationships among these strains all were probed for the presence of an O-methyltransferase gene specific to this biosynthetic pathway. Among the strains of interest, only Streptomyces hygroscopicus subsp. yakushimaensis, the patent strain for FK520/FK523, failed to hybridize with the probes.
Garrity
G M
GM
Basic Microbiology Department, Merck Research Laboratories, Merck & Co., Rahway, NJ 07065.
Heimbuch
B K
BK
Motamedi
H
H
Shafiee
A
A
D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D002849:Chromatography, Gas; D015342:DNA Probes; D004269:DNA, Bacterial / Q000737:chemistry; D003960:Diaminopimelic Acid / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis; D005798:Genes, Bacterial; D007166:Immunosuppressive Agents; D008780:Methyltransferases / Q000235:genetics; D010641:Phenotype; D011090:Polyenes; D012689:Sequence Homology, Nucleic Acid; D020123:Sirolimus; D013302:Streptomyces / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives
D000900:Anti-Bacterial Agents; D015342:DNA Probes; D004269:DNA, Bacterial; D005227:Fatty Acids; D007166:Immunosuppressive Agents; D011090:Polyenes; D003960:Diaminopimelic Acid; C058028:immunomycin; C082701:FK506 methyltransferase; C082704:FK520 methyltransferase; D008780:Methyltransferases; D020123:Sirolimus; D016559:Tacrolimus