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Genetic relationships among actinomycetes that produce the immunosuppressant macrolides FK506, FK520/FK523 and rapamycin
Authors:George M Garrity  Brain K Heimbuch  Haideh Motamedi  Ali Shafiee
Institution:(1) Basic Microbiology Department, Merck Research Laboratories Merck & Co., Rahway, NJ, USA;(2) Molecular Genetics and Microbial Chemotherapeutics Department, Merck Research Laboratories, Merck & Co., Rahway, NJ, USA;(3) Fermentation Microbiology Department, Merck Research Laboratories, Merck & Co., Rahway, NJ, USA;(4) Microbial Resources Group, Merck & Co., 07065 Rahway, NJ, USA
Abstract:Summary 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 ofStreptomyces with 16ratio0 and 15ratio0anteiso predominating. Principal component analysis of GC data revealed distinct profiles for each culture. Reciprocal DNA homology studies atT m -25 showed the rapamycin-producing strain and one FK506-producing strain to have 38–50% homology with the type strain ofStreptomyces 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 anO-methyltransferase gene specific to this biosynthetic pathway. Among the strains of interest, onlyStreptomyces hygroscopicus subsp.yakushimaensis, the patent strain for FK520/FK523, failed to hybridize with the probes.
Keywords:Immunosuppressant  FK506  FK520  FK523  Rapamycin  Ascomycin  Immunomycin  Streptomyces  Taxonomy  Gene probes
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