Regulation of specialised metabolites in Actinobacteria – expanding the paradigms

Environmental Microbiology Reports

Volumn 10, Issue 3, 2018, Pages 231-238

  Hoskisson, Paul A ^a   Fernández Martínez, Lorena T ^b  

^a UNIVERSITY OF STRATHCLYDE   (United Kingdom)

^b EDGE HILL UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL FACTOR;

ACTINOBACTERIA; BIOSYNTHESIS; GENE EXPRESSION REGULATION; GENETICS; MULTIGENE FAMILY;

ACTINOBACTERIA; BIOLOGICAL FACTORS; BIOSYNTHETIC PATHWAYS; GENE EXPRESSION REGULATION, BACTERIAL; MULTIGENE FAMILY;

EID: 85044864874     PISSN: None     EISSN: 17582229     Source Type: Journal    
DOI: 10.1111/1758-2229.12629     Document Type: Review

References (79)

1. Al-Bassam, M.M., Bibb, M.J., Bush, M.J., Chandra, G., and Buttner, M.J. (2014) Response regulator heterodimer formation controls a key stage in Streptomyces development. PLoS Genet 10: e1004554.
2. Alexander, D.C., and Jensen, S.E. (1998) Investigation of the Streptomyces clavuligerus cephamycin C gene cluster and its regulation by the CcaR protein. J Bacteriol 180: 4068–4079.
3. Allenby, N.E.E., Laing, E., Bucca, G., Kierzek, A.M., and Smith, C.P. (2012) Diverse control of metabolism and other cellular processes in Streptomyces coelicolor by the PhoP transcription factor: genome-wide identification of in vivo targets. Nucleic Acids Res 40: 9543–9556.
4. Anderson, T.B., Brian, P., and Champness, W.C. (2001) Genetic and transcriptional analysis of absA, an antibiotic gene cluster-linked two-component system that regulates multiple antibiotics in Streptomyces coelicolor. Mol Microbiol 39: 553–566.
5. Behie, S.W., Bonet, B., Zacharia, V.M., McClung, D.J., and Traxler, M.F. (2017) Molecules to ecosystems: actinomycete natural products in situ. Front Microbiol 7: 2149.
6. Bibb, M.J. (2013) Understanding and manipulating antibiotic production in actinomycetes. Biochem Soc Trans 41: 1355–1364. doi:10.1042/BST20130214.
7. Bibb, M.J. (2005) Regulation of secondary metabolism in streptomycetes. Curr Opin Microbiol 8: 208–215.
8. Cangelosi, G.A., Do, J.S., Freeman, R., Bennett, J.G., Semret, M., and Behr, M.A. (2006) The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium. Antimicrob Agents Chemother 50: 461–468.
9. Cashel, M., Gentry, D.R., Hernandez, V.H., and Vinella, D. (1996) The stringent response. In Bacterial Stress Responses. 2nd ed. Neidhardt, F.C., Curtiss III, R., Ingraham J.L., Lin, E.C.C., Low, K.B., Magasanik, B., et al. (eds). Washington, DC: ASM Press.
10. Chakraburtty, R., and Bibb, M. (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.
11. Chandra, G., and Chater, K.F. (2008) Evolutionary flux of potentially bldA-dependent Streptomyces genes containing the rare leucine codon TTA. Antonie Van Leeuwenhoek 94: 111–126.
12. Chng, C., Lum, A.M., Vroom, J.A., and Kao, C.M. (2008) A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea. Proc Natl Acad Sci USA 105: 11346–11351.
13. Clark, L.C., Seipke, R.F., Prieto, P., Willemse, J., van Wezel, G.P., Hutchings, M.I., and Hoskisson, P.A. (2013) Mammalian cell entry genes in Streptomyces may provide clues to the evolution of bacterial virulence. Sci Rep 3: 1109.
14. Daniel-Ivad, M., Hameed, N., Tan, S., Dhanjal, R., et al. (2017) An engineered allele of afsQ1 facilitates the discovery and investigation of cryptic natural products. ACS Chem Biol 12: 628–634.
15. Den Hengst, C.D., Tran, N.T., Bibb, M.J., Chandra, G., Leskiw, B.K., and Buttner, M.J. (2010) Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Mol Microbiol 78: 361–379.
16. Elliot, M., Damji, F., Passantino, R., Chater, K., and Leskiw, B. (1998) The bldD gene of Streptomyces coelicolor A3(2): a regulatory gene involved in morphogenesis and antibiotic production. J Bacteriol 180: 1549–1555.
17. Elliot, M.A., and Leskiw, B.K. (1999) The BldD protein from Streptomyces coelicolor is a DNA-binding protein. J Bacteriol 181: 6832–6835.
18. Elliot, M.A., Bibb, M.J., Buttner, M.J., and Leskiw, B.K. (2001) BldD is a direct regulator of key developmental genes in Streptomyces coelicolor A3(2). Mol Microbiol 40: 257–269.
19. Fernández-Martínez, L.T., Gomez-Escribano, J.P., and Bibb, M.J. (2015) A relA-dependent regulatory cascade for auto-induction of microbisporicin production in Microbispora corallina. Mol Microbiol 97: 502–514.
20. Floriano, B., and Bibb, M. (1996) afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2). Mol Microbiol 21: 385–396.
21. Foulston, L., and Bibb, M. (2011) Feed-forward regulation of microbisporicin biosynthesis in Microbispora corallina. J Bacteriol 193: 3064–3071.
22. Foulston, L.C., and Bibb, M.J. (2010) Microbisporicin gene cluster reveals unusual features of lantibiotic biosynthesis in actinomycetes. Proc Natl Acad Sci USA 107: 13461–13466.
23. Gomez-Escribano, J.P., and Bibb, M.J. (2011) Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters. Microb Biotechnol 4: 207–215.
24. He, J.-M., Zhu, H., Zheng, G.-S., Liu, P.-P., Wang, J., and Zhao, G.-P. (2016) Direct involvement of the master nitrogen metabolism regulator GlnR in antibiotic biosynthesis in Streptomyces. J Biol Chem 291: 26443–26454.
25. Helmann, J.D. (2002) The extracytoplasmic function (ECF) sigma factors. Adv Microb Physiol 46: 47–110.
26. Hesketh, A., Sun, J., and Bibb, M. (2001) Induction of ppGpp synthesis in Streptomyces coelicolor A3(2) grown under conditions of nutritional sufficiency elicits actII-ORF4 transcription and actinorhodin biosynthesis. Mol Microbiol 39: 136–144.
27. Hiltner, J.K., Hunter, I.S., and Hoskisson, P.A. (2015) Tailoring specialized metabolite production in Streptomyces. Adv Appl Microbiology 91: 237–255.
28. Horinouchi, S. (2003) AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2). J Ind Microbiol Biotechnol 30: 462–467.
29. Horinouchi, S., and Beppu, T. (1994) A-factor as a microbial hormone that controls cellular differentiation and secondary metabolism in Streptomyces griseus. Mol Microbiol 12: 859–864.
30. Horinouchi, S., Kito, M., Nishiyama, M., Furuya, K., Hong, S.K., Miyake, K., and Beppu, T. (1990) Primary structure of AfsR, a global regulatory protein for secondary metabolite formation in Streptomyces coelicolor A3(2). Gene 95: 49–56.
31. Hoskisson, P.A., and Hutchings, M.I. (2006) MtrAB–LpqB: a conserved three-component system in actinobacteria? Trends Microbiol 14: 444–449.
32. Hou, B., Lin, Y., Wu, H., Guo, M., Petkovic, H., Tao, L., et al. (2018) The novel transcriptional regulator LmbU promotes lincomycin biosynthesis through regulating expression of its target genes in Streptomyces lincolnensis. J Bacteriol 200. pii: e00447–17. doi:10.1128/JB.00447-17.
33. Hsiao, N.-H., Soding, J., Linke, D., Lange, C., Hertweck, C., Wohlleben, W., and Takano, E. (2007) ScbA from Streptomyces coelicolor A3(2) has homology to fatty acid synthases and is able to synthesize gamma-butyrolactones. Microbiology 153: 1394–1404.
34. Huang, J., Shi, J., Molle, V., Sohlberg, B., Weaver, D., Bibb, M.J., et al. (2005) Cross-regulation among disparate antibiotic biosynthetic pathways of Streptomyces coelicolor. Mol Microbiol 58: 1276–1287.
35. Huang, X., Pinto, D., Fritz, G., and Mascher, T. (2015) Environmental Sensing in Actinobacteria: a Comprehensive Survey on the Signaling Capacity of This Phylum. J Bacteriol 197: 2517–2535.
36. Huang, Y., Yang, D., Pan, G., Tang, G.-L., and Shen, B. (2016) Characterization of LnmO as a pathway-specific Crp/Fnr-type positive regulator for leinamycin biosynthesis in Streptomyces atroolivaceus and its application for titer improvement. Appl Microbiol Biotechnol 100: 10555–10562.
37. Hutchings, M.I., Hoskisson, P.A., Chandra, G., and Buttner, M.J. (2004) Sensing and responding to diverse extracellular signals? Analysis of the sensor kinases and response regulators of Streptomyces coelicolor A3(2). Microbiology 150: 2795–2806.
38. Ishizuka, H., Horinouchi, S., Kieser, H.M., Hopwood, D.A., and Beppu, T. (1992) A putative two-component regulatory system involved in secondary metabolism in Streptomyces spp. J Bacteriol 174: 7585–7594.
39. Le Maréchal, P., Decottignies, P., Marchand, C.H., Degrouard, J., et al. (2013) Comparative proteomic analysis of Streptomyces lividans wild-type and ppk mutant strains reveals the importance of storage lipids for antibiotic biosynthesis. Appl Environ Microbiol 79: 5907–5917.
40. Liao, C.-H., Yao, L., Xu, Y., Liu, W.-B., Zhou, Y., and Ye, B.-C. (2015) Nitrogen regulator GlnR controls uptake and utilization of non-phosphotransferase-system carbon sources in actinomycetes. Proc Natl Acad Sci USA 111: 15630–15635.
41. Liu, G., Chater, K.F., Chandra, G., Niu, G., and Tan, H. (2013) Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiol Mol Biol Rev 77: 112–143.
42. Maharjan, S., Oh, T.-J., Lee, H.C., and Sohng, J.K. (2009) Identification and functional characterization of an afsR homolog regulatory gene from Streptomyces venezuelae ATCC 15439. J Microbiol Biotechnol 19: 121–127.
43. Martín, J.F., Rodríguez-García, A., and Liras, P. (2017) The master regulator PhoP coordinates phosphate and nitrogen metabolism, respiration, cell differentiation and antibiotic biosynthesis: comparison in Streptomyces coelicolor and Streptomyces avermitilis. J Antibiot 70: 534–541.
44. McLean, T.C., Hoskisson, P.A., and Seipke, R.F. (2016) Coordinate regulation of antimycin and candicidin biosynthesis. mSphere 1: e00305-16.
45. Möker, N., Brocker, M., Schaffer, S., Krämer, R., Morbach, S., and Bott, M. (2004) Deletion of the genes encoding the MtrA-MtrB two-component system of Corynebacterium glutamicum has a strong influence on cell morphology, antibiotics susceptibility and expression of genes involved in osmoprotection. Mol Microbiol 54: 420–438.
46. Nieselt, K., Battke, F., Herbig, A., Bruheim, P., Wentzel, A., Jakobsen, Ø.M., et al. (2010) The dynamic architecture of the metabolic switch in Streptomyces coelicolor. BMC Genomics 11: 10.
47. O'Rourke, S., Widdick, D., and Bibb, M. (2017) A novel mechanism of immunity controls the onset of cinnamycin biosynthesis in Streptomyces cinnamoneus DSM 40646. J Ind Microbiol Biotechnol 44: 563–572.
48. Parajuli, N., Viet, H.T., Ishida, K., Tong, H.T., Lee, H.C., Liou, K., and Sohng, J.K. (2005) Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952. Res Microbiol 156: 707–712.
49. Pérez-Llarena, F.J., Liras, P., Rodríguez-García, A., and Martín, J.F. (1997) A regulatory gene (ccaR) required for cephamycin and clavulanic acid production in Streptomyces clavuligerus: amplification results in overproduction of both beta-lactam compounds. J Bacteriol 179: 2053–2059.
50. Rodríguez-García, A., Barreiro, C., Santos-Beneit, F., Sola-Landa, A., and Martín, J.F. (2007) Genome-wide transcriptomic and proteomic analysis of the primary response to phosphate limitation in Streptomyces coelicolor M145 and in a ΔphoP mutant. Proteomics 7: 2410–2429.
51. Ryding, N.J., Anderson, T.B., and Champness, W.C. (2002) Regulation of the Streptomyces coelicolor calcium-dependent antibiotic by absA, encoding a cluster-linked two-component system. J Bacteriol 184: 794–805.
52. Santamarta, I., López-García, M.T., Kurt, A., Nárdiz, N., Álvarez-Álvarez, R., Pérez-Redondo, R., et al. (2011) Characterization of DNA-binding sequences for CcaR in the cephamycin-clavulanic acid supercluster of Streptomyces clavuligerus. Mol Microbiol 81: 968–981.
53. Santos-Beneit, F., Rodriguez-Garcia, A., Sola-Landa, A., and Martin, J.F. (2009) Cross-talk between two global regulators in Streptomyces: PhoP and AfsR interact in the control of afsS, pstS and phoRP transcription. Mol Microbiol 72: 53–68.
54. Schniete, J.K., Cruz-Morales, P., Selem-Mojica, N., Fernández-Martínez, L.T., Hunter, I.S., Barona-Gómez, F., and Hoskisson, P.A. (2018) Expanding primary metabolism helps generate the metabolic robustness to facilitate antibiotic biosynthesis in Streptomyces. mBio 9: e02283–17.
55. Seipke, R.F., and Hutchings, M.I. (2013) The regulation and biosynthesis of antimycins. Beilstein J Org Chem 9: 2556–2563.
56. Seipke, R.F., Patrick, E., and Hutchings, M.I. (2014) Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σAntA. PeerJ 2: e253.
57. Sherwood, E.J., and Bibb, M.J. (2013) The antibiotic planosporicin coordinates its own production in the actinomycete Planomonospora alba. Proc Natl Acad Sci USA 110: E2500–E2509.
58. Sidda, J.D., and Corre, C. (2012) Gamma-butyrolactone and furan signaling systems in Streptomyces. Methods Enzymol 517: 71–87.
59. Som, N.F., Heine, D., Holmes, N.A., Munnoch, J.T., Chandra, G., and Seipke, R.F. (2017a) The conserved actinobacterial two-component system MtrAB coordinates chloramphenicol production with sporulation in Streptomyces venezuelae NRRL B-65442. Front Microbiol 8: 1145.
60. Som, N.F., Heine, D., Holmes, N., Knowles, F., Chandra, G., Seipke, R.F., et al. (2017b) The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2). Microbiology 163: 1415–1419.
61. Staroń, A., Sofia, H.J., Dietrich, S., Ulrich, L.E., Liesegang, H., and Mascher, T. (2009) The third pillar of bacterial signal transduction: classification of the extracytoplasmic function (ECF) σ factor protein family. Mol Microbiol 74: 557–581.
62. St-Onge, R.J., and Elliot, M.A. (2017) Regulation of a muralytic enzyme-encoding gene by two non-coding RNAs. RNA Biol 14:1592–1605.
63. St-Onge, R.J., Haiser, H.J., Yousef, M.R., Sherwood, E., Tschowri, N., Al-Bassam, M., and Elliot, M.A. (2015) Nucleotide second messenger-mediated regulation of a muralytic enzyme in Streptomyces. Mol Microbiol 96: 779–795.
64. Stubbendieck, R.M., Vargas-Bautista, C., and Straight, P.D. (2016) Bacterial communities: interactions to scale. Front Microbiol 7: 13.
65. Traxler, M.F., Kolter, R., Kinkel, L.L., Wang, J., Zheng, H., Wang, Y., et al. (2015) Natural products in soil microbe interactions and evolution. Nat Prod Rep 32: 956–970.
66. Tschowri, N. (2016) Cyclic dinucleotide-controlled regulatory pathways in Streptomyces species. J Bacteriol 198: 47–54.
67. Ueda, K., Takano, H., Nishimoto, M., Inaba, H., and Beppu, T. (2005) Dual transcriptional control of amfTSBA, which regulates the onset of cellular differentiation in Streptomyces griseus. J Bacteriol 187: 135–142.
68. Urem, M., Świątek-Połatyńska, M.A., Rigali, S., and van Wezel, G.P. (2016) Intertwining nutrient-sensory networks and the control of antibiotic production in Streptomyces. Mol Microbiol 102: 183–195.
69. Van Wezel, G.P., and Mcdowall, K.J. (2011) The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep 28: 1311–1333.
70. Vargas-Bautista, C., Rahlwes, K., and Straight, P. (2014) Bacterial competition reveals differential regulation of the pks genes by Bacillus subtilis. J Bacteriol 196: 717–728.
71. Via, L.E., Curcic, R., Mudd, M.H., Dhandayuthapani, S., Ulmer, R.J., and Deretic, V. (1996) Elements of signal transduction in Mycobacterium tuberculosis: in vitro phosphorylation and in vivo expression of the response regulator MtrA. J Bacteriol 178: 3314–3321.
72. Ward, J.M., and Hodgson, J.E. (1993) The biosynthetic genes for clavulanic acid and cephamycin production occur as a “super-cluster” in three Streptomyces. FEMS Microbiol Lett 110: 239–242.
73. Watve, M., Tickoo, R., Jog, M., and Bhole, B. (2001) How many antibiotics are produced by the genus Streptomyces? Arch Microbiol 176: 386–390.
74. Wang, R., Mast, Y., Wang, J., Zhang, W., et al. (2013) Identification of two-component system AfsQ1/Q2 regulon and its cross-regulation with GlnR in Streptomyces coelicolor. Mol Microbiol 87: 30–48.
75. White, J., and Bibb, M. (1997) bldA dependence of undecylprodigiosin production in Streptomyces coelicolor A3(2) involves a pathway-specific regulatory cascade. J Bacteriol 179: 627–633.
76. Wietzorrek, A., and Bibb, M. (1997) A novel family of proteins that regulates antibiotic production in streptomycetes appears to contain an OmpR-like DNA-binding fold. Mol Microbiol 25: 1181–1184.
77. Yang, D., Rateb, M.E., Wang, N., and Shen, B. (2017) Competition and co-regulation of spirotoamide and tautomycetin biosynthesis in Streptomyces griseochromogenes, and isolation and structural elucidation of spirotoamide C and D. J Antibiot 70: 710–714.
78. Yao, L.L., and Ye, B.C. (2016). Reciprocal regulation of GlnR and PhoP in response to nitrogen and phosphate limitations in Saccharopolyspora erythraea. Appl Environ Microbiol 82: 409–420.
79. Yao, L.-L., Liao, C.-H., Huang, G., Zhou, Y., Rigali, S., Zhang, B., and Ye, B.-C. (2014) GlnR-mediated regulation of nitrogen metabolism in the actinomycete Saccharopolyspora erythraea. Appl Microbiol Biotechnol 98: 7935–7948.