GENETIC-RELATIONSHIPS AMONG ACTINOMYCETES THAT PRODUCE THE IMMUNOSUPPRESSANT MACROLIDES FK506, FK520 FK523 AND RAPAMYCIN/

A polyphasic taxonomic study was undertaken to establish the genetic a nd phenotypic relationships among six actinomycetes that produce the i mmunosuppressant macrolides FK506, FK520/FK523 and rapamycin. Chemotax onomic studies reveal that all have Type I cell walls. Gas chromatogra phy (GC) of fatty acid methyl esters revealed patterns consisted for s trains of Streptomyces with 16 : 0 and 15 : 0 anteiso predominating. P rincipal component analysis of GC data revealed distinct profiles for each culture. Reciprocal DNA homology studies at T(m)-25 showed the ra pamycin-producing strain and one FK506-producing strain to have 38-50% homology with the type strain of Streptomyces hygroscopicus (ATCC 274 38). The remaining strains exhibited 6-17% homology. To further explor e the relationships among these strains all were probed for the presen ce of an O-methyltransferase gene specific to this biosynthetic pathwa y. Among the strains of interest, only Streptomyces hygroscopicus subs p. yakushimaensis, the patent strain for FK520/FK523, failed to hybrid ize with the probes.