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.