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. 1997 Feb;179(3):627–633. doi: 10.1128/jb.179.3.627-633.1997

bldA dependence of undecylprodigiosin production in Streptomyces coelicolor A3(2) involves a pathway-specific regulatory cascade.

J White 1, M Bibb 1
PMCID: PMC178740  PMID: 9006013

Abstract

The production of the red-pigmented tripyrrole antibiotic undecylprodigiosin (Red) by Streptomyces coelicolor A3(2) depends on two pathway-specific regulatory genes, redD and redZ. RedD is homologous to several other proteins that regulate antibiotic production in streptomycetes; RedZ is a member of the response regulator family. redZ transcripts were detected during exponential growth and increased in amount during transition and stationary phases; transcription of redD was confined to the two latter stages of growth. Whereas mutation of redD had no effect on redZ transcription, transcription of redD was highly dependent on redZ, suggesting that RedZ is a transcriptional activator of redD. bldA, which encodes the only tRNA of S. coelicolor that can efficiently translate the rare leucine codon UUA, is required for Red production at higher phosphate concentrations. While the redD transcript contains no UUA codons, the redZ mRNA contains one. Transcription of redZ appeared to be unaffected in a bldA mutant; in contrast, redD transcription was undetectable, consistent with the translational dependence of redZ on bldA and the transcriptional dependence of redD on redZ. Red production in a bldA mutant was restored by multiple copies of redZ, presumably reflecting a low level of mistranslation of the redZ UUA codon, while multiple copies of redD had no effect, presumably a consequence of the severe dependence of redD transcription on RedZ. Transcription of redZ appears to be negatively autoregulated.

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Selected References

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  1. Bierman M., Logan R., O'Brien K., Seno E. T., Rao R. N., Schoner B. E. Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene. 1992 Jul 1;116(1):43–49. doi: 10.1016/0378-1119(92)90627-2. [DOI] [PubMed] [Google Scholar]
  2. Brown K. L., Wood S., Buttner M. J. Isolation and characterization of the major vegetative RNA polymerase of Streptomyces coelicolor A3(2); renaturation of a sigma subunit using GroEL. Mol Microbiol. 1992 May;6(9):1133–1139. doi: 10.1111/j.1365-2958.1992.tb01551.x. [DOI] [PubMed] [Google Scholar]
  3. Bruton C. J., Guthrie E. P., Chater K. F. Phage vectors that allow monitoring of transcription of secondary metabolism genes in Streptomyces. Biotechnology (N Y) 1991 Jul;9(7):652–656. doi: 10.1038/nbt0791-652. [DOI] [PubMed] [Google Scholar]
  4. Buttner M. J., Chater K. F., Bibb M. J. Cloning, disruption, and transcriptional analysis of three RNA polymerase sigma factor genes of Streptomyces coelicolor A3(2). J Bacteriol. 1990 Jun;172(6):3367–3378. doi: 10.1128/jb.172.6.3367-3378.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chakraburtty R., White J., Takano E., Bibb M. Cloning, characterization and disruption of a (p)ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2). Mol Microbiol. 1996 Jan;19(2):357–368. doi: 10.1046/j.1365-2958.1996.390919.x. [DOI] [PubMed] [Google Scholar]
  6. Chater K. F., Bruton C. J., King A. A., Suarez J. E. The expression of Streptomyces and Escherichia coli drug-resistance determinants cloned into the Streptomyces phage phi C31. Gene. 1982 Jul-Aug;19(1):21–32. doi: 10.1016/0378-1119(82)90185-8. [DOI] [PubMed] [Google Scholar]
  7. Chater K. F. The improving prospects for yield increase by genetic engineering in antibiotic-producing Streptomycetes. Biotechnology (N Y) 1990 Feb;8(2):115–121. doi: 10.1038/nbt0290-115. [DOI] [PubMed] [Google Scholar]
  8. Clayton T. M., Bibb M. J. Streptomyces promoter-probe plasmids that utilise the xylE gene of Pseudomonas putida. Nucleic Acids Res. 1990 Feb 25;18(4):1077–1077. doi: 10.1093/nar/18.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coco E. A., Narva K. E., Feitelson J. S. New classes of Streptomyces coelicolor A3(2) mutants blocked in undecylprodigiosin (Red) biosynthesis. Mol Gen Genet. 1991 May;227(1):28–32. doi: 10.1007/BF00260702. [DOI] [PubMed] [Google Scholar]
  10. Feitelson J. S., Hopwood D. A. Cloning of a Streptomyces gene for an O-methyltransferase involved in antibiotic biosynthesis. Mol Gen Genet. 1983;190(3):394–398. doi: 10.1007/BF00331065. [DOI] [PubMed] [Google Scholar]
  11. Feitelson J. S., Malpartida F., Hopwood D. A. Genetic and biochemical characterization of the red gene cluster of Streptomyces coelicolor A3(2). J Gen Microbiol. 1985 Sep;131(9):2431–2441. doi: 10.1099/00221287-131-9-2431. [DOI] [PubMed] [Google Scholar]
  12. Fernández-Moreno M. A., Caballero J. L., Hopwood D. A., Malpartida F. The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. Cell. 1991 Aug 23;66(4):769–780. doi: 10.1016/0092-8674(91)90120-n. [DOI] [PubMed] [Google Scholar]
  13. Floriano B., Bibb M. afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2). Mol Microbiol. 1996 Jul;21(2):385–396. doi: 10.1046/j.1365-2958.1996.6491364.x. [DOI] [PubMed] [Google Scholar]
  14. Furuya K., Hutchinson C. R. The DnrN protein of Streptomyces peucetius, a pseudo-response regulator, is a DNA-binding protein involved in the regulation of daunorubicin biosynthesis. J Bacteriol. 1996 Nov;178(21):6310–6318. doi: 10.1128/jb.178.21.6310-6318.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gramajo H. C., Takano E., Bibb M. J. Stationary-phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated. Mol Microbiol. 1993 Mar;7(6):837–845. doi: 10.1111/j.1365-2958.1993.tb01174.x. [DOI] [PubMed] [Google Scholar]
  16. Guthrie E. P., Chater K. F. The level of a transcript required for production of a Streptomyces coelicolor antibiotic is conditionally dependent on a tRNA gene. J Bacteriol. 1990 Nov;172(11):6189–6193. doi: 10.1128/jb.172.11.6189-6193.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hopwood D. A., Chater K. F., Bibb M. J. Genetics of antibiotic production in Streptomyces coelicolor A3(2), a model streptomycete. Biotechnology. 1995;28:65–102. doi: 10.1016/b978-0-7506-9095-9.50009-5. [DOI] [PubMed] [Google Scholar]
  18. Janssen G. R., Bibb M. J. Derivatives of pUC18 that have BglII sites flanking a modified multiple cloning site and that retain the ability to identify recombinant clones by visual screening of Escherichia coli colonies. Gene. 1993 Feb 14;124(1):133–134. doi: 10.1016/0378-1119(93)90774-w. [DOI] [PubMed] [Google Scholar]
  19. Janssen G. R., Ward J. M., Bibb M. J. Unusual transcriptional and translational features of the aminoglycoside phosphotransferase gene (aph) from Streptomyces fradiae. Genes Dev. 1989 Mar;3(3):415–429. doi: 10.1101/gad.3.3.415. [DOI] [PubMed] [Google Scholar]
  20. Larson J. L., Hershberger C. L. The minimal replicon of a streptomycete plasmid produces an ultrahigh level of plasmid DNA. Plasmid. 1986 May;15(3):199–209. doi: 10.1016/0147-619x(86)90038-7. [DOI] [PubMed] [Google Scholar]
  21. Lawlor E. J., Baylis H. A., Chater K. F. Pleiotropic morphological and antibiotic deficiencies result from mutations in a gene encoding a tRNA-like product in Streptomyces coelicolor A3(2). Genes Dev. 1987 Dec;1(10):1305–1310. doi: 10.1101/gad.1.10.1305. [DOI] [PubMed] [Google Scholar]
  22. Leskiw B. K., Bibb M. J., Chater K. F. The use of a rare codon specifically during development? Mol Microbiol. 1991 Dec;5(12):2861–2867. doi: 10.1111/j.1365-2958.1991.tb01845.x. [DOI] [PubMed] [Google Scholar]
  23. Leskiw B. K., Lawlor E. J., Fernandez-Abalos J. M., Chater K. F. TTA codons in some genes prevent their expression in a class of developmental, antibiotic-negative, Streptomyces mutants. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2461–2465. doi: 10.1073/pnas.88.6.2461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MacNeil D. J., Occi J. L., Gewain K. M., MacNeil T., Gibbons P. H., Ruby C. L., Danis S. J. Complex organization of the Streptomyces avermitilis genes encoding the avermectin polyketide synthase. Gene. 1992 Jun 15;115(1-2):119–125. doi: 10.1016/0378-1119(92)90549-5. [DOI] [PubMed] [Google Scholar]
  25. Madduri K., Hutchinson C. R. Functional characterization and transcriptional analysis of the dnrR1 locus, which controls daunorubicin biosynthesis in Streptomyces peucetius. J Bacteriol. 1995 Mar;177(5):1208–1215. doi: 10.1128/jb.177.5.1208-1215.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Malpartida F., Niemi J., Navarrete R., Hopwood D. A. Cloning and expression in a heterologous host of the complete set of genes for biosynthesis of the Streptomyces coelicolor antibiotic undecylprodigiosin. Gene. 1990 Sep 1;93(1):91–99. doi: 10.1016/0378-1119(90)90141-d. [DOI] [PubMed] [Google Scholar]
  27. Murray M. G. Use of sodium trichloroacetate and mung bean nuclease to increase sensitivity and precision during transcript mapping. Anal Biochem. 1986 Oct;158(1):165–170. doi: 10.1016/0003-2697(86)90605-6. [DOI] [PubMed] [Google Scholar]
  28. Narva K. E., Feitelson J. S. Nucleotide sequence and transcriptional analysis of the redD locus of Streptomyces coelicolor A3(2). J Bacteriol. 1990 Jan;172(1):326–333. doi: 10.1128/jb.172.1.326-333.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Oh S. H., Chater K. F. Denaturation of circular or linear DNA facilitates targeted integrative transformation of Streptomyces coelicolor A3(2): possible relevance to other organisms. J Bacteriol. 1997 Jan;179(1):122–127. doi: 10.1128/jb.179.1.122-127.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Otten S. L., Ferguson J., Hutchinson C. R. Regulation of daunorubicin production in Streptomyces peucetius by the dnrR2 locus. J Bacteriol. 1995 Mar;177(5):1216–1224. doi: 10.1128/jb.177.5.1216-1224.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rudd B. A., Hopwood D. A. A pigmented mycelial antibiotic in Streptomyces coelicolor: control by a chromosomal gene cluster. J Gen Microbiol. 1980 Aug;119(2):333–340. doi: 10.1099/00221287-119-2-333. [DOI] [PubMed] [Google Scholar]
  32. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  33. Stutzman-Engwall K. J., Otten S. L., Hutchinson C. R. Regulation of secondary metabolism in Streptomyces spp. and overproduction of daunorubicin in Streptomyces peucetius. J Bacteriol. 1992 Jan;174(1):144–154. doi: 10.1128/jb.174.1.144-154.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Takano E., Gramajo H. C., Strauch E., Andres N., White J., Bibb M. J. Transcriptional regulation of the redD transcriptional activator gene accounts for growth-phase-dependent production of the antibiotic undecylprodigiosin in Streptomyces coelicolor A3(2). Mol Microbiol. 1992 Oct;6(19):2797–2804. doi: 10.1111/j.1365-2958.1992.tb01459.x. [DOI] [PubMed] [Google Scholar]
  35. Tsao S. W., Rudd B. A., He X. G., Chang C. J., Floss H. G. Identification of a red pigment from Streptomyces coelicolor A3(2) as a mixture of prodigiosin derivatives. J Antibiot (Tokyo) 1985 Jan;38(1):128–131. doi: 10.7164/antibiotics.38.128. [DOI] [PubMed] [Google Scholar]

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