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. 1982 May;21(5):758–763. doi: 10.1128/aac.21.5.758

S-Adenosyl-L-methionine: macrocin O-methyltransferase activities in a series of Streptomyces fradiae mutants that produce different levels of the macrolide antibiotic tylosin.

E T Seno, R H Baltz
PMCID: PMC182007  PMID: 7103455

Abstract

A series of mutants of Streptomyces fradiae selected for increased production of the macrolide antibiotic tylosin was analyzed for levels of expression of macrocin O-methyltransferase, the enzyme which catalyzes the final step in the biosynthesis of tylosin. Increased tylosin production was accompanied by increased macrocin O-methyltransferase in some of the mutants. Increased expression of macrocin O-methyltransferase was due to more rapid early biosynthesis of the enzyme, to reduced decay of enzyme specific activity late in the fermentation, or to combinations of both. Mutant strains which showed rapid loss of enzyme specific activity late in the fermentation converted large amounts of tylosin to relomycin. The most productive mutants, which synthesized elevated levels of macrocin O-methyltransferase, also produced large amounts of macrocin, the substrate for the enzyme. Incomplete conversion of macrocin to tylosin by these mutants may be due to substrate and product inhibition (E. T. Seno and R. H. Baltz, Antimicrob. Agents Chemother. 20:370-377, 1981). The results suggest that both the levels of precursors and the levels of expression of tylosin biosynthetic enzymes are important for efficient production of tylosin.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baltz R. H. Genetic recombination in Streptomyces fradiae by protoplast fusion and cell regeneration. J Gen Microbiol. 1978 Jul;107(1):93–102. doi: 10.1099/00221287-107-1-93. [DOI] [PubMed] [Google Scholar]
  2. Baltz R. H. Genetics and biochemistry on tylosin production: a model for genetic engineering in antibiotic-producing Streptomyces. Basic Life Sci. 1982;19:431–444. doi: 10.1007/978-1-4684-4142-0_32. [DOI] [PubMed] [Google Scholar]
  3. Baltz R. H., Seno E. T. Properties of Streptomyces fradiae mutants blocked in biosynthesis of the macrolide antibiotic tylosin. Antimicrob Agents Chemother. 1981 Aug;20(2):214–225. doi: 10.1128/aac.20.2.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bibb M. J., Ward J. M., Hopwood D. A. Transformation of plasmid DNA into Streptomyces at high frequency. Nature. 1978 Jul 27;274(5669):398–400. doi: 10.1038/274398a0. [DOI] [PubMed] [Google Scholar]
  5. Bibb M., Schottel J. L., Cohen S. N. A DNA cloning system for interspecies gene transfer in antibiotic-producing Streptomyces. Nature. 1980 Apr 10;284(5756):526–531. doi: 10.1038/284526a0. [DOI] [PubMed] [Google Scholar]
  6. Hopwood D. A., Wright H. M. Bacterial protoplast fusion: recombination in fused protoplasts of Streptomyces coelicolor. Mol Gen Genet. 1978 Jul 4;162(3):307–317. doi: 10.1007/BF00268856. [DOI] [PubMed] [Google Scholar]
  7. Hopwood D. A., Wright H. M., Bibb M. J., Cohen S. N. Genetic recombination through protoplast fusion in Streptomyces. Nature. 1977 Jul 14;268(5616):171–174. doi: 10.1038/268171a0. [DOI] [PubMed] [Google Scholar]
  8. Hopwood D. A., Wright H. M. Factors affecting recombinant frequency in protoplast fusions of Streptomyces coelicolor. J Gen Microbiol. 1979 Mar;111(1):137–143. doi: 10.1099/00221287-111-1-137. [DOI] [PubMed] [Google Scholar]
  9. Ochi K., Hitchcock M. J., Katz E. High-frequency fusion of Streptomyces parvulus or Streptomyces antibioticus protoplasts induced by polyethylene glycol. J Bacteriol. 1979 Sep;139(3):984–992. doi: 10.1128/jb.139.3.984-992.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Seno E. T., Baltz R. H. Properties of S-adenosyl-L-methionine:macrocin O-methyltransferase in extracts of Streptomyces fradiae strains which produce normal or elevated levels of tylosin and in mutants blocked in specific O-methylations. Antimicrob Agents Chemother. 1981 Sep;20(3):370–377. doi: 10.1128/aac.20.3.370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Seno E. T., Pieper R. L., Huber F. M. Terminal stages in the biosynthesis of tylosin. Antimicrob Agents Chemother. 1977 Mar;11(3):455–461. doi: 10.1128/aac.11.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Suarez J. E., Chater K. F. DNA cloning in Streptomyces: a bifunctional replicon comprising pBR322 inserted into a Streptomyces phage. Nature. 1980 Jul 31;286(5772):527–529. doi: 10.1038/286527a0. [DOI] [PubMed] [Google Scholar]
  13. Thompson C. J., Ward J. M., Hopwood D. A. DNA cloning in Streptomyces: resistance genes from antibiotic-producing species. Nature. 1980 Jul 31;286(5772):525–527. doi: 10.1038/286525a0. [DOI] [PubMed] [Google Scholar]

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