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 16 0 and 15 0anteiso 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. |
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Keywords: | Immunosuppressant FK506 FK520 FK523 Rapamycin Ascomycin Immunomycin Streptomyces Taxonomy Gene probes |
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