Genetic relationships among actinomycetes that produce the immunosuppressant macrolides FK506, FK520/FK523 and rapamycin |
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Authors: | George M Garrity Brain K Heimbuch Haideh Motamedi Ali Shafiee |
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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 |
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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 160 and 150anteiso predominating. Principal component analysis of GC data revealed distinct profiles for each culture. Reciprocal DNA homology studies atT
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-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. |
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Keywords: | Immunosuppressant FK506 FK520 FK523 Rapamycin Ascomycin Immunomycin Streptomyces Taxonomy Gene probes |
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