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PMID: 20204454 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genetic factors that influence moenomycin production in streptomycetes.

Journal of industrial microbiology & biotechnology ·Vol. 37 ·No. 6 ·2010-06-00 ·Pages 559-66

Makitrynskyy R, Rebets Y, Ostash B, Zaburannyi N, Rabyk M, Walker S, Fedorenko V

Abstract

Moenomycin, a natural phosphoglycolipid product that has a long history of use in animal nutrition, is currently considered an attractive starting point for the development of novel antibiotics. We recently reconstituted the biosynthesis of this natural product in a heterologous host, Streptomyces lividans TK24, but production levels were too low to be useful. We have examined several other streptomycetes strains as hosts and have also explored the overexpression of two pleiotropic regulatory genes, afsS and relA, on moenomycin production. A moenomycin-resistant derivative of S. albus J1074 was found to give the highest titers of moenomycin, and production was improved by overexpressing relA. Partial duplication of the moe cluster 1 in S. ghanaensis also increased average moenomycin production. The results reported here suggest that rational manipulation of global regulators combined with increased moe gene dosage could be a useful technique for improvement of moenomycin biosynthesis.

MeSH Terms
Animals Anti-Bacterial Agents/biosynthesis,isolation & purification Bambermycins/biosynthesis,isolation & purification Carbohydrate Sequence Cloning, Molecular Gene Dosage Gene Expression Regulation, Bacterial Genes, Regulator Molecular Sequence Data Streptomyces/genetics,metabolism Streptomyces lividans/genetics,metabolism
Chemicals
Anti-Bacterial Agents Bambermycins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Makitrynskyy Roman
Department of Genetics and Biotechnology, Ivan Franko National University of L'viv, Grushevskogo st. 4, L'viv 79005, Ukraine.
Rebets Yuriy
Ostash Bohdan
Zaburannyi Nestor
Rabyk Mariia
Walker Suzanne
Fedorenko Victor
References (29)
29 references, click to expand
  1. Phosphorylated AbsA2 negatively regulates antibiotic production in Streptomyces coelicolor through interactions with pathway-specific regulatory gene promoters.
    J Bacteriol. 2007 Jul;189(14):5284-92 PMID: 17513473
  2. Regulation of secondary metabolism in streptomycetes.
    Curr Opin Microbiol. 2005 Apr;8(2):208-15 PMID: 15802254
  3. Structural analysis of the contacts anchoring moenomycin to peptidoglycan glycosyltransferases and implications for antibiotic design.
    ACS Chem Biol. 2008 Jul 18;3(7):429-36 PMID: 18642800
  4. Characterization of a negative regulator AveI for avermectin biosynthesis in Streptomyces avermitilis NRRL8165.
    Appl Microbiol Biotechnol. 2008 Aug;80(2):277-86 PMID: 18560830
  5. Bacterial transglycosylase inhibitors.
    Curr Opin Chem Biol. 2005 Oct;9(5):459-66 PMID: 16118062
  6. The total synthesis of moenomycin A.
    J Am Chem Soc. 2006 Nov 29;128(47):15084-5 PMID: 17117848
  7. Antibacterial activity of synthetic analogues based on the disaccharide structure of moenomycin, an inhibitor of bacterial transglycosylase.
    Microbiology. 2000 Dec;146 Pt 12:3129-40 PMID: 11101671
  8. Inhibition of transglycosylation involved in bacterial peptidoglycan synthesis.
    Curr Med Chem. 2000 Aug;7(8):801-20 PMID: 10828288
  9. Genetic manipulation of antibiotic-producing Streptomyces.
    Trends Microbiol. 1998 Feb;6(2):76-83 PMID: 9507643
  10. [Analysis of genome rearrangements in Streptomyces kanamyceticus mutants].
    Antibiot Khimioter. 1998;43(4):14-9 PMID: 9606499
  11. afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2).
    Mol Microbiol. 1996 Jul;21(2):385-96 PMID: 8858592
  12. Identifying bacterial genes and endosymbiont DNA with Glimmer.
    Bioinformatics. 2007 Mar 15;23(6):673-9 PMID: 17237039
  13. Streptomyces albus G mutants defective in the SalGI restriction-modification system.
    J Gen Microbiol. 1980 Feb;116(2):323-34 PMID: 6246193
  14. Coordination of export and glycosylation of landomycins in Streptomyces cyanogenus S136.
    FEMS Microbiol Lett. 2008 Aug;285(2):195-202 PMID: 18537830
  15. Complete characterization of the seventeen step moenomycin biosynthetic pathway.
    Biochemistry. 2009 Sep 22;48(37):8830-41 PMID: 19640006
  16. Cross-regulation among disparate antibiotic biosynthetic pathways of Streptomyces coelicolor.
    Mol Microbiol. 2005 Dec;58(5):1276-87 PMID: 16313616
  17. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  18. Induction of actinorhodin production by rpsL (encoding ribosomal protein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2).
    J Bacteriol. 1996 Dec;178(24):7276-84 PMID: 8955413
  19. Effect of a global regulatory gene, afsR2, from Streptomyces lividans on avermectin production in Streptomyces avermitilis.
    J Biosci Bioeng. 2000;89(6):606-8 PMID: 16232806
  20. Identification and characterization of Streptomyces ghanaensis ATCC14672 integration sites for three actinophage-based plasmids.
    Plasmid. 2009 May;61(3):171-5 PMID: 19167423
  21. A gene transfer system for the glycopeptide producer Nonomuraea sp. ATCC39727.
    FEMS Microbiol Lett. 2003 Aug 8;225(1):53-7 PMID: 12900021
  22. A streamlined metabolic pathway for the biosynthesis of moenomycin A.
    Chem Biol. 2007 Mar;14(3):257-67 PMID: 17379141
  23. Functional analysis of relA and rshA, two relA/spoT homologues of Streptomyces coelicolor A3(2).
    J Bacteriol. 2001 Jun;183(11):3488-98 PMID: 11344157
  24. Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis.
    Science. 2007 Mar 9;315(5817):1402-5 PMID: 17347437
  25. Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2).
    BMC Genomics. 2008;9:56 PMID: 18230178
  26. The biosynthetic gene cluster for the antitumor rebeccamycin: characterization and generation of indolocarbazole derivatives.
    Chem Biol. 2002 Apr;9(4):519-31 PMID: 11983340
  27. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 PMID: 10829079
  28. afsR2: a previously undetected gene encoding a 63-amino-acid protein that stimulates antibiotic production in Streptomyces lividans.
    Mol Microbiol. 1994 Nov;14(4):643-53 PMID: 7891553
  29. Amplification of the entire kanamycin biosynthetic gene cluster during empirical strain improvement of Streptomyces kanamyceticus.
    Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9661-6 PMID: 16766657
Article Info
Journal
Journal of industrial microbiology & biotechnology
Abbr.
J Ind Microbiol Biotechnol
ISSN
1476-5535
Published
2010-06-00
Epub
2010-00-06
Pages
559-66
Language
English
Region
Germany
NLM ID
9705544
PMCID
PMC2939378
Subset
IM
Grants
NIGMS NIH HHS · R01 GM076710-04 · United States
NIAID NIH HHS · R01 AI050855 · United States
NCRR NIH HHS · P41 RR015301-075426 · United States
NIAID NIH HHS · R01 AI050855-06 · United States
NIAID NIH HHS · AI50855 · United States
NIGMS NIH HHS · R01 GM076710 · United States
NIAID NIH HHS · P01 AI083214 · United States
NIAID NIH HHS · P01 AI083214-026668 · United States
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