Abstract
The wblA gh gene, encoding a homologue of the WhiB-family of proteins, was identified in the sequenced genome of moenomycin producer Streptomyces ghanaensis. Deletion of the gene blocked aerial mycelium sporulation and caused a 230% increase in moenomycins production. S. ghanaensis overexpressing SSFG-01620: a homologue of extracellular protease inhibitor SCO0762, whose expression in Streptomyces coelicolor is down-regulated by wblA: showed deficiencies in sporulation similar to that of wblA gh knockout strain. The wblA gh gene of S. ghanaensis appears to play a negative role in the control of moenomycin biosynthesis and is essential for sporulation.
Similar content being viewed by others
References
Aínsa JA, Bird N, Ryding NJ, Findlay KC, Chater KF (2010) The complex whiJ locus mediates environmentally sensitive repression of development of Streptomyces coelicolor A3 (2). Antonie Van Leeuwenhoek 98:225–236
Alam MS, Garg SK, Agrawal P (2007) Molecular function of WhiB4/Rv3681c of Mycobacterium tuberculosis H37Rv: a [4Fe–4S] cluster co-ordinating protein disulphide reductase. Mol Microbiol 63:1414–1431
Datsenko KA, Wanner BL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 97:6640–6645
den Hengst CD, Buttner MJ (2008) Redox control in actinobacteria. Biochim Biophys Acta 1780:1201–1216
Fowler-Goldsworthy K, Gust B, Mouz S, Chandra G, Findlay KC, Chater KF (2011) The actinobacteria-specific gene wblA controls major developmental transitions in Streptomyces coelicolor A3 (2). Microbiology 157:1312–1328
Gust B, Chandra G, Jakimowicz D, Yuqing T, Bruton CJ, Chater KF (2004) Lambda red-mediated genetic manipulation of antibiotic-producing Streptomyces. Adv Appl Microbiol 54:107–128
Halliday J, McKeveney D, Muldoon C, Rajaratnam P, Meutermans W (2006) Targeting the forgotten transglycosylases. Biochem Pharmacol 71:957–967
Kang SH, Huang J, Lee HN, Hur YA, Cohen SN, Kim ES (2007) Interspecies DNA microarray analysis identifies WblA as a pleiotropic down-regulator of antibiotic biosynthesis in Streptomyces. J Bacteriol 189:4315–4319
Kieser T, Bibb M, Buttner M, Chater K, Hopwood D (2000) Practical Streptomyces genetics. The John Innes Foundation, Norwich
Kim DW, Hesketh A, Kim ES, Song JY, Lee DH, Kim IS, Chater KF, Lee KJ (2008) Complex extracellular interactions of proteases and a protease inhibitor influence multicellular development of Streptomyces coelicolor. Mol Microbiol 70:1180–1193
Makitrynskyy R, Rebets Y, Ostash B, Zaburannyi N, Rabyk M, Walker S, Fedorenko V (2010) Genetic factors that influence moenomycin production in streptomycetes. J Ind Microbiol Biotechnol 37:559–566
Noh JH, Kim SH, Lee HN, Lee SY, Kim ES (2010) Isolation and genetic manipulation of the antibiotic down-regulatory gene, WblA ortholog for doxorubicin-producing Streptomyces strain improvement. Appl Microbiol Biotechnol 86:1145–1153
Ostash B, Walker S (2010) Moenomycin family antibiotics: chemical synthesis, biosynthesis, and biological activity. Nat Prod Rep 27:1594–1617
Pfaller MA (2006) Flavophospholipol use in animals: positive implications for antimicrobial resistance based on its microbiologic properties. Diagn Microbiol Infect Dis 56:115–121
Sambrook J, Russell WD (2001) Molecular cloning: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
van Wezel GP, McKenzie NL, Nodwell JR (2009) Chapter 5. Applying the genetics of secondary metabolism in model actinomycetes to the discovery of new antibiotics. Methods Enzymol 458:117–141
Acknowledgments
This work was supported by grant Bg-01F from Ministry of education, science, youth and sport of Ukraine (to V. F.), and NIH grant 5R01GM076710 (to S. W.). We thank John Santa Maria (Harvard Medical School, USA) for careful reading of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Rabyk, M., Ostash, B., Rebets, Y. et al. Streptomyces ghanaensis pleiotropic regulatory gene wblA gh influences morphogenesis and moenomycin production. Biotechnol Lett 33, 2481–2486 (2011). https://doi.org/10.1007/s10529-011-0728-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-011-0728-z