Decreased Growth and Antibiotic Production in Streptomyces coelicolor A3(2) by Deletion of a Highly Conserved DeoR Family Regulator, SCO1463

Springer Science and Business Media LLC - Tập 24 - Trang 613-621 - 2019
Jong-Min Jeon1, Tae-Rim Choi1, Bo-Rahm Lee1, Joo-Hyun Seo2, Hun-Suk Song1, Hye-Rim Jung1, Soo-Yeon Yang1, Jun Young Park1, Eun-Jung Kim3, Byung-Gee Kim3, Yung-Hun Yang1,4
1Department of Microbial Engineering, College of Engineering, Konkuk University, Seoul, Korea
2Department of Bio and Fermentation Convergence Technology & BK21 Plus Project, Kookmin University, Seoul, Korea
3School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea
4Institute for Ubiquitous Information Technology and Applications, Konkuk University, Seoul, Korea

Tóm tắt

Streptomyces spp. have been isolated from different environmental niches and are known to exhibit diversity in secondary metabolism. They have complex regulation system to control secondary metabolism, however it is difficult to prioritize the importance of specific regulator among the thousands of global or cluster-situated genes that may regulate secondary metabolism in different Streptomyces strains. Here we suggest a simple homology-based selection method to find out important regulators by comparing seven Streptomyces strains finding highly homologous regulators in various Streptomyces strains and showed highly homologous 11 regulators containing four well known regulators such as BldM, IclR, WhiD and NdgR. Among various regulators, we showed a putative transcriptional regulator in Streptomyces coelicolor A3(2), SCO1463 playing a pivotal role in growth, antibiotic production (actinorhodin[ACT] and undecylprodigiosin [RED] production), and production/utilization of organic acids such as propionate and succinate by making comparisons between the deletion mutant and the wild type strain. Although high homology in various strains does not always mean the importance of a gene, we suggested a criterion on which regulator should be studied first and which would be more important among more than one thousand regulators.

Tài liệu tham khảo

Trepanier, N. K., S. E. Jensen, D. C. Alexander, and B. K. Leskiw (2002) The positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus is mistranslated in a bldA mutant. Microbiology. 148: 643–656. Sanchez, S., A. Chavez, A. Forero, Y. Garcia-Huante, A. Romero, M. Sanchez, D. Rocha, B. Sanchez, M. Avalos, S. Guzman-Trampe, R. Rodriguez-Sanoja, E. Langley, and B. Ruiz (2010) Carbon source regulation of antibiotic production. J. Antibiot. 63: 442–459. Grimm, H. (1996) Comparative in vitro studies on the beta-lactamase-inhibiting effect of clavulanic acid and sulbactam on ampicillin-resistant Enterobacteriaceae. Int. J. Antimicrob. Agents. 6: S9–S14. Abou-Zeid, A. Z. and A. I. el-Dewany (1973) Production and biosynthesis of puromycin by Streptomyces alboniger. Zentralbl Bakteriol Parasitenkd Infektionskr Hyg. 128: 635–659. Bibb, M. J. (2005) Regulation of secondary metabolism in streptomycetes. Curr. Opin. Microbiol. 8: 208–215. Chakraburtty, R. and M. Bibb (1997) The ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2) plays a conditional role in antibiotic production and morphological differentiation. J. Bacteriol. 179: 5854–5861. Jin, W., H. K. Kim, J. Y. Kim, S. G. Kang, S. H. Lee, and K. J. Lee (2004) Cephamycin C production is regulated by relA and rsh genes in Streptomyces clavuligerus ATCC27064. J. Biotechnol. 114: 81–87. Horinouchi, S. and T. Beppu (1992) Regulation of secondary metabolism and cell differentiation in Streptomyces: A-factor as a microbial hormone and the AfsR protein as a component of a two-component regulatory system. Gene. 115: 167–172. Kitani, S., Y. Yamada, and T. Nihira (2001) Gene replacement analysis of the butyrolactone autoregulator receptor (FarA) reveals that FarA acts as a Novel regulator in secondary metabolism of Streptomyces lavendulae FRI-5. J. Bacteriol. 183: 4357–4363. Bate, N., A. R. Butler, A. R. Gandecha, and E. Cundliffe (1999) Multiple regulatory genes in the tylosin biosynthetic cluster of Streptomyces fradiae. Chem. Biol. 6: 617–624. Anton, N., M. V. Mendes, J. F. Martin, and J. F. Aparicio (2004) Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis. J. Bacteriol. 186: 2567–2575. Ryding, N. J., T. B. Anderson, and W. C. Champness (2002) Regulation of the Streptomyces coelicolor calcium-dependent antibiotic by absA, encoding a cluster-linked two-component system. J. Bacteriol. 184: 794–805. Santamarta, I., A. Rodriguez-Garcia, R. Perez-Redondo, J. F. Martin, and P. Liras (2002) CcaR is an autoregulatory protein that binds to the ccaR and cefD-cmcI promoters of the cephamycin C-clavulanic acid cluster in Streptomyces clavuligerus. J. Bacteriol. 184: 3106–3113. Romero-Rodriguez, A., I. Robledo-Casados, and S. Sanchez (2015) An overview on transcriptional regulators in Streptomyces. Biochim. Biophys. Acta. 1849: 1017–1039. Okada, U., K. Kondo, T. Hayashi, N. Watanabe, M. Yao, T. Tamura, and I. Tanaka (2008) Structural and functional analysis of the TetR-family transcriptional regulator SCO0332 from Streptomyces coelicolor. Acta Crystallogr. D Biol. Crystallogr 64: 198–205. Park, S. S., Y. H. Yang, E. Song, E. J. Kim, W. S. Kim, J. K. Sohng, H. C. Lee, K. K. Liou, and B. G. Kim (2009) Mass spectrometric screening of transcriptional regulators involved in antibiotic biosynthesis in Streptomyces coelicolor A3(2). J. Ind. Microbiol. Biotechnol. 36: 1073–1083. Chng, C., A. M. Lum, J. A. Vroom, and C. M. Kao (2008) A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea. Proc. Natl. Acad. Sci. U.S.A. 105: 11346–11351. Chater, K. F. (2016) Recent advances in understanding Streptomyces. F1000Res. 5: 2795. Blair, J. M., M. A. Webber, A. J. Baylay, D. O. Ogbolu, and L. J. Piddock (2015) Molecular mechanisms of antibiotic resistance. Nat Rev. Microbiol. 13: 42–51. Molina-Henares, A. J., T. Krell, M. Eugenia Guazzaroni, A. Segura, and J. L. Ramos (2006) Members of the IclR family of bacterial transcriptional regulators function as activators and/or repressors. FEMS Microbiol. Rev. 30: 157–186. Kieser, T., M. J. Bibb, M. J. Buttner, K. F. Chater, and D. A. Hopwood (2000) Practical Streptomyces Genetics. pp. 43–60. John Innes Foundation, Norwich, UK. Kim, M., J. S. Yi, J. Kim, J. N. Kim, M. W. Kim, and B. G. Kim (2014) Reconstruction of a high-quality metabolic model enables the identification of gene overexpression targets for enhanced antibiotic production in Streptomyces coelicolor A3(2). Biotechnol. J. 9: 1185–1194. Bierman, M., R. Logan, K. O’Brien, E. T. Seno, R. N. Rao, and B. E. Schoner (1992) Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene. 116: 43–49. Bystrykh, L. V., M. A. Fernandez-Moreno, J. K. Herrema, F. Malpartida, D. A. Hopwood, and L. Dijkhuizen (1996) Production of actinorhodin-related “blue pigments” by Streptomyces coelicolor A3(2). J. Bacteriol. 178: 2238–2244. Yang, Y. H., E. Song, E. J. Kim, K. Lee, W. S. Kim, S. S. Park, J. S. Hahn, and B. G. Kim (2009) NdgR, an IclR-like regulator involved in amino-acid-dependent growth, quorum sensing, and antibiotic production in Streptomyces coelicolor. Appl. Microbiol Biotechnol. 82: 501–511. Jeon, J. M., H. Park, H. M. Seo, J. H. Kim, S. K. Bhatia, G. Sathiyanarayanan, H. S. Song, S. H. Park, K. Y. Choi, B. I. Sang, and Y. H. Yang (2015) Isobutanol production from an engineered Shewanella oneidensis MR-1. Bioprocess Biosyst. Eng. 38: 2147–2154. Hara, H., Y. Ohnishi, and S. Horinouchi (2009) DNA microarray analysis of global gene regulation by A-factor in Streptomyces griseus. Microbiology. 155: 2197–2210. Chater, K. F. (2001) Regulation of sporulation in Streptomyces coelicolor A3(2): a checkpoint multiplex? Curr. Opin. Microbiol. 4: 667–673. Saxild, H. H., L. N. Andersen, and K. Hammer (1996) dra-nupC-pdp operon of Bacillus subtilis: nucleotide sequence, induction by deoxyribonucleosides, and transcriptional regulation by the deoR-encoded DeoR repressor protein. J. Bacteriol. 178: 424–434. Ulanova, D., S. Kitani, E. Fukusaki, and T. Nihira (2013) SdrA, a new DeoR family regulator involved in Streptomyces avermitilis morphological development and antibiotic production. Appl. Environ. Microbiol. 79: 7916–7921. Ge B., Y. Liu, B. Liu, W. Zhao, and K. Zhang (2016) Characterization of novel DeoR-family member from the Streptomyces ahygroscopicus strain CK-15 that acts as a repressor of morphological development. Appl. Microbiol. Biotechnol. 100: 8819–8828. Gust, B., G. L. Challis, K. Fowler, T. Kieser, and K. F. Chater (2003) PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc. Natl. Acad. Sci. U.S.A. 100: 1541–1546. Zhang, P., L. Wu, Y. Zhu, M. Liu, Y. Wang, G. Cao, X. L. Chen, M. Tao, and X. Pang (2017) Deletion of MtrA inhibits cellular development of Streptomyces coelicolor and alters expression of developmental regulatory genes. Front. Microbiol. 8: 2013. Liangzhi, L., H. Zheng, and Y. Yingjin (2007) Effect of propionate on streptolydigin production and carbon flux distribution in Streptomyces lydicus AS 4.2501. Chin. J. Chem. Eng. 15: 143–149. Yu, L., Y. Pan, and G. Liu (2016) A Regulatory gene SCO2140 is involved in antibiotic production and morphological differentiation of Streptomyces coelicolor A3(2). Curr Microbiol. 73: 196–201. Hillerich, B. and J. Westpheling (2006) A new GntR family transcriptional regulator in Streptomyces coelicolor is required for morphogenesis and antibiotic production and controls transcription of an ABC transporter in response to carbon source. J. Bacteriol. 188: 7477–7487. Molle, V., W. J. Palframan, K. C. Findlay, and M. J. Buttner (2000) WhiD and WhiB, homologous proteins required for different stages of sporulation in Streptomyces coelicolor A3(2). J. Bacteriol. 182: 1286–1295.