Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus

Journal of Industrial Microbiology and Biotechnology

Volumn 43, Issue 4, 2016, Pages 537-555

  Ferguson, Nicole L ^a   Peña Castillo, Lourdes ^a   Moore, Marcus A ^a   Bignell, Dawn R D ^a   Tahlan, Kapil ^a  

^a MEMORIAL UNIVERSITY OF NEWFOUNDLAND   (Canada)

Author keywords

Biosynthesis; Clavulanic acid; iTRAQ; Proteomics; Regulation; Secondary metabolism; Streptomyces clavuligerus

Indexed keywords

CLAVULANIC ACID; PROTEOME; TRANSFER RNA; BACTERIAL PROTEIN; BETA LACTAMASE INHIBITOR; CODON;

ARTICLE; BACTERIAL STRAIN; BACTERIUM MUTANT; COMPARATIVE STUDY; MORPHOLOGY; NONHUMAN; PROTEIN EXPRESSION; PROTEOMICS; STREPTOMYCES CLAVULIGERUS; WILD TYPE; BIOSYNTHESIS; CODON; GENE EXPRESSION REGULATION; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; STREPTOMYCES;

BACTERIAL PROTEINS; BETA-LACTAMASE INHIBITORS; CLAVULANIC ACID; CODON; GENE EXPRESSION REGULATION, BACTERIAL; PROTEOME; PROTEOMICS; STREPTOMYCES;

EID: 84961141212     PISSN: 13675435     EISSN: 14765535     Source Type: Journal    
DOI: 10.1007/s10295-016-1733-y     Document Type: Article

References (109)

1. Ainsa 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
2. Alexander DC, Jensen SE (1998) Investigation of the Streptomyces clavuligerus cephamycin C gene cluster and its regulation by the CcaR protein. J Bacteriol 180:4068–4079
3. Alvarez-Alvarez R, Rodriguez-Garcia A, Santamarta I, Perez-Redondo R, Prieto-Dominguez A, Martinez-Burgo Y, Liras P (2014) Transcriptomic analysis of Streptomyces clavuligerus Delta-ccaR:tsr: effects of the cephamycin C-clavulanic acid cluster regulator CcaR on global regulation. Microb Biotechnol 7:221–231
4. Belcourt MF, Farabaugh PJ (1990) Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site. Cell 62:339–352
5. Benjamini YaH Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodol) 57:289–300
6. Benson AK, Haldenwang WG (1993) Bacillus subtilis sigma B is regulated by a binding protein (RsbW) that blocks its association with core RNA polymerase. Proc Natl Acad Sci USA 90:2330–2334
7. Bentley PH, Berry PD, Brooks G, Gilpin ML, Hunt E, Zomaya II (1977) Total synthesis of (±)-clavulanic acid. J Chem Soc Chem Commun 748–749
8. Bibb MJ (2005) Regulation of secondary metabolism in streptomycetes. Curr Opin Microbiol 8:208–215
9. Bibb MJ, Molle V, Buttner MJ (2000) Sigma(BldN), an extracytoplasmic function RNA polymerase sigma factor required for aerial mycelium formation in Streptomyces coelicolor A3(2). J Bacteriol 182:4606–4616
10. Bignell DR, Lau LH, Colvin KR, Leskiw BK (2003) The putative anti–anti-sigma factor BldG is post-translationally modified by phosphorylation in Streptomyces coelicolor. FEMS Microbiol Lett 225:93–99
11. Bignell DR, Tahlan K, Colvin KR, Jensen SE, Leskiw BK (2005) Expression of ccaR, encoding the positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus, is dependent on bldG. Antimicrob Agents Chemother 49:1529–1541
12. Bignell DR, Warawa JL, Strap JL, Chater KF, Leskiw BK (2000) Study of the bldG locus suggests that an anti–anti-sigma factor and an anti-sigma factor may be involved in Streptomyces coelicolor antibiotic production and sporulation. Microbiology 146(Pt 9):2161–2173
13. Boehm AM, Putz S, Altenhofer D, Sickmann A, Falk M (2007) Precise protein quantification based on peptide quantification using iTRAQ. BMC Bioinform 8:214. doi:10.1186/1471-2105-8-214
14. Brekasis D, Paget MS (2003) A novel sensor of NADH/NAD + redox poise in Streptomyces coelicolor A3(2). EMBO J 22:4856–4865
15. Brierley I, Jenner AJ, Inglis SC (1992) Mutational analysis of the “slippery-sequence” component of a coronavirus ribosomal frameshifting signal. J Mol Biol 227:463–479
16. Brown D, Evans JR, Fletton RA (1979) Structures of three novel beta-lactams isolated from Streptomyces clavuligerus. Chem Commun 6:282–283
17. Buttner MJ, Chater KF, Bibb MJ (1990) Cloning, disruption, and transcriptional analysis of three RNA polymerase sigma factor genes of Streptomyces coelicolor A3(2). J Bacteriol 172:3367–3378
18. Casado-Vela J, Martinez-Esteso MJ, Rodriguez E, Borras E, Elortza F, Bru-Martinez R (2010) iTRAQ-based quantitative analysis of protein mixtures with large fold change and dynamic range. Proteomics 10:343–347
19. Chen GF, Inouye M (1990) Suppression of the negative effect of minor arginine codons on gene expression; preferential usage of minor codons within the first 25 codons of the Escherichia coli genes. Nucleic Acids Res 18:1465–1473
20. den Hengst CD, Tran NT, Bibb MJ, Chandra G, Leskiw BK, Buttner MJ (2010) Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Mol Microbiol 78:361–379
21. Duncan L, Losick R (1993) SpoIIAB is an anti-sigma factor that binds to and inhibits transcription by regulatory protein sigma F from Bacillus subtilis. Proc Natl Acad Sci USA 90:2325–2329
22. Eccleston M, Ali RA, Seyler R, Westpheling J, Nodwell J (2002) Structural and genetic analysis of the BldB protein of Streptomyces coelicolor. J Bacteriol 184:4270–4276
23. Eccleston M, Willems A, Beveridge A, Nodwell JR (2006) Critical residues and novel effects of overexpression of the Streptomyces coelicolor developmental protein BldB: evidence for a critical interacting partner. J Bacteriol 188:8189–8195
24. Elliot M, Damji F, Passantino R, Chater K, 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
25. Elliot MA, Bibb MJ, Buttner MJ, Leskiw BK (2001) BldD is a direct regulator of key developmental genes in Streptomyces coelicolor A3(2). Mol Microbiol 40:257–269
26. Fang H, Gough J (2013) DcGO: database of domain-centric ontologies on functions, phenotypes, diseases and more. Nucleic Acids Res 41:D536–D544
27. Fernandez-Moreno MA, Caballero JL, Hopwood DA, Malpartida F (1991) The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. Cell 66:769–780
28. Fernandez-Moreno MA, Martin-Triana AJ, Martinez E, Niemi J, Kieser HM, Hopwood DA, Malpartida F (1992) abaA, a new pleiotropic regulatory locus for antibiotic production in Streptomyces coelicolor. J Bacteriol 174:2958–2967
29. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014) Pfam: the protein families database. Nucleic Acids Res 42:D222–D230
30. Floriano B, 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
31. Foulstone M, Reading C (1982) Assay of amoxicillin and clavulanic acid, the components of Augmentin, in biological fluids with high-performance liquid chromatography. Antimicrob Agents Chemother 22:753–762
32. Ghorbel S, Kormanec J, Artus A, Virolle MJ (2006) Transcriptional studies and regulatory interactions between the phoR–phoP operon and the phoU, mtpA, and ppk genes of Streptomyces lividans TK24. J Bacteriol 188:677–686
33. Guthrie EP, Chater KF (1990) The level of a transcript required for production of a Streptomyces coelicolor antibiotic is conditionally dependent on a tRNA gene. J Bacteriol 172:6189–6193
34. Hempel AM, Cantlay S, Molle V, Wang SB, Naldrett MJ, Parker JL, Richards DM, Jung YG, Buttner MJ, Flardh K (2012) The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces. Proc Natl Acad Sci USA 109:E2371–E2379
35. Hopwood DA (1967) Genetic analysis and genome structure in Streptomyces coelicolor. Bacteriol Rev 31:373–403
36. Horinouchi S, Hara O, Beppu T (1983) Cloning of a pleiotropic gene that positively controls biosynthesis of A-factor, actinorhodin, and prodigiosin in Streptomyces coelicolor A3(2) and Streptomyces lividans. J Bacteriol 155:1238–1248
37. Huang D, Xia M, Li S, Wen J, Jia X (2013) Enhancement of FK506 production by engineering secondary pathways of Streptomyces tsukubaensis and exogenous feeding strategies. J Ind Microbiol Biotechnol 40:1023–1037
38. Hunt AC, Servin-Gonzalez L, Kelemen GH, Buttner MJ (2005) The bldC developmental locus of Streptomyces coelicolor encodes a member of a family of small DNA-binding proteins related to the DNA-binding domains of the MerR family. J Bacteriol 187:716–728
39. Hutchings MI, Hong HJ, Buttner MJ (2006) The vancomycin resistance VanRS two-component signal transduction system of Streptomyces coelicolor. Mol Microbiol 59:923–935
40. Jayapal KP, Philp RJ, Kok YJ, Yap MG, Sherman DH, Griffin TJ, Hu WS (2008) Uncovering genes with divergent mRNA-protein dynamics in Streptomyces coelicolor. PLoS One 3:e2097. doi:10.1371/journal.pone.0002097
41. Jensen SE (2012) Biosynthesis of clavam metabolites. J Ind Microbiol Biotechnol 39:1407–1419
42. Jensen SE, Paradkar AS, Mosher RH, Anders C, Beatty PH, Brumlik MJ, Griffin A, Barton B (2004) Five additional genes are involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. Antimicrob Agents Chemother 48:192–202
43. Kelemen GH, Brown GL, Kormanec J, Potuckova L, Chater KF, Buttner MJ (1996) The positions of the sigma-factor genes, whiG and sigF, in the hierarchy controlling the development of spore chains in the aerial hyphae of Streptomyces coelicolor A3(2). Mol Microbiol 21:593–603
44. Kelemen GH, Buttner MJ (1998) Initiation of aerial mycelium formation in Streptomyces. Curr Opin Microbiol 1:656–662
45. Kelemen GH, Viollier PH, Tenor J, Marri L, Buttner MJ, Thompson CJ (2001) A connection between stress and development in the multicellular prokaryote Streptomyces coelicolor A3(2). Mol Microbiol 40:804–814
46. Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical Streptomyces genetics. John Innes Centre, Norwich
47. Kwak J, Kendrick KE (1996) Bald mutants of Streptomyces griseus that prematurely undergo key events of sporulation. J Bacteriol 178:4643–4650
48. Lawlor EJ, Baylis HA, Chater KF (1987) Pleiotropic morphological and antibiotic deficiencies result from mutations in a gene encoding a tRNA-like product in Streptomyces coelicolor A3(2). Genes Dev 1:1305–1310
49. Lebrihi A, Germain D, Lefebvre G (1987) Phosphate repression of cephamycin and clavulanic acid production by Streptomyces clavuligerus. Appl Microbiol Biotechnol 26:130–135
50. Lee Y, Kim K, Suh JW, Rhee S, Lim Y (2007) Binding study of AfsK, a Ser/Thr kinase from Streptomyces coelicolor A3(2) and S-adenosyl-l-methionine. FEMS Microbiol Lett 266:236–240
51. Leskiw BK, Lawlor EJ, Fernandez-Abalos JM, Chater KF (1991) TTA codons in some genes prevent their expression in a class of developmental, antibiotic-negative, Streptomyces mutants. Proc Natl Acad Sci USA 88:2461–2465
52. Lopez-Garcia MT, Santamarta I, Liras P (2010) Morphological differentiation and clavulanic acid formation are affected in a Streptomyces clavuligerusadpA-deleted mutant. Microbiology 156:2354–2365
53. Manteca A, Sanchez J, Jung HR, Schwammle V, Jensen ON (2010) Quantitative proteomics analysis of Streptomyces coelicolor development demonstrates that onset of secondary metabolism coincides with hypha differentiation. Mol Cell Proteom 9:1423–1436
54. Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV, Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C, Bryant SH (2011) CDD: a conserved domain database for the functional annotation of proteins. Nucleic Acids Res 39:D225–D229
55. Martin JF (2004) Phosphate control of the biosynthesis of antibiotics and other secondary metabolites is mediated by the PhoR–PhoP system: an unfinished story. J Bacteriol 186:5197–5201
56. Martinez-Burgo Y, Alvarez-Alvarez R, Rodriguez-Garcia A, Liras P (2015) The pathway-specific regulator ClaR of Streptomyces clavuligerus has a global effect on the expression of genes for secondary metabolism and differentiation. Appl Environ Microbiol 81:6637–6648
57. McCormick JR, Flardh K (2012) Signals and regulators that govern Streptomyces development. FEMS Microbiol Rev 36:206–231
58. Medema MH, Trefzer A, Kovalchuk A, van den Berg M, Muller U, Heijne W, Wu L, Alam MT, Ronning CM, Nierman WC, Bovenberg RA, Breitling R, Takano E (2010) The sequence of a 1.8-mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways. Genome Biol Evol 2:212–224
59. Merrick MJ (1976) A morphological and genetic mapping study of bald colony mutants of Streptomyces coelicolor. J Gen Microbiol 96:299–315
60. Mingyar E, Sevcikova B, Rezuchova B, Homerova D, Novakova R, Kormanec J (2014) The sigma(F)-specific anti-sigma factor RsfA is one of the protein kinases that phosphorylates the pleiotropic anti–anti-sigma factor BldG in Streptomyces coelicolor A3(2). Gene 538:280–287
61. Molle V, Buttner MJ (2000) Different alleles of the response regulator gene bldM arrest Streptomyces coelicolor development at distinct stages. Mol Microbiol 36:1265–1278
62. Navone L, Casati P, Licona-Cassani C, Marcellin E, Nielsen LK, Rodriguez E, Gramajo H (2014) Allantoin catabolism influences the production of antibiotics in Streptomyces coelicolor. Appl Microbiol Biotechnol 98:351–360
63. Nguyen KT, Tenor J, Stettler H, Nguyen LT, Nguyen LD, Thompson CJ (2003) Colonial differentiation in Streptomyces coelicolor depends on translation of a specific codon within the adpA gene. J Bacteriol 185:7291–7296
64. Paget MS, Chamberlin L, Atrih A, Foster SJ, Buttner MJ (1999) Evidence that the extracytoplasmic function sigma factor sigma E is required for normal cell wall structure in Streptomyces coelicolor A3(2). J Bacteriol 181:204–211
65. Paget MS, Kang JG, Roe JH, Buttner MJ (1998) Sigma R, an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2). EMBO J 17:5776–5782
66. Paradkar A (2013) Clavulanic acid production by Streptomyces clavuligerus: biogenesis, regulation and strain improvement. J Antibiot (Tokyo) 66:411–420
67. Paradkar AS, Aidoo KA, Jensen SE (1998) A pathway-specific transcriptional activator regulates late steps of clavulanic acid biosynthesis in Streptomyces clavuligerus. Mol Microbiol 27:831–843
68. Paradkar AS, Jensen SE (1995) Functional analysis of the gene encoding the clavaminate synthase 2 isoenzyme involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. J Bacteriol 177:1307–1314
69. Parashar A, Colvin KR, Bignell DR, Leskiw BK (2009) BldG and SCO3548 interact antagonistically to control key developmental processes in Streptomyces coelicolor. J Bacteriol 191:2541–2550
70. Perez-Llarena FJ, Liras P, Rodriguez-Garcia A, Martin JF (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
71. Persson J, Chater KF, Flardh K (2013) Molecular and cytological analysis of the expression of Streptomyces sporulation regulatory gene whiH. FEMS Microbiol Lett 341:96–105
72. Piret JM, Chater KF (1985) Phage-mediated cloning of bldA, a region involved in Streptomyces coelicolor morphological development, and its analysis by genetic complementation. J Bacteriol 163:965–972
73. Pope MK, Green B, Westpheling J (1998) The bldB gene encodes a small protein required for morphogenesis, antibiotic production, and catabolite control in Streptomyces coelicolor. J Bacteriol 180:1556–1562
74. Price B, Adamidis T, Kong R, Champness W (1999) A Streptomyces coelicolor antibiotic regulatory gene, absB, encodes an RNase III homolog. J Bacteriol 181:6142–6151
75. Rajkarnikar A, Kwon HJ, Ryu YW, Suh JW (2006) Catalytic domain of AfsKav modulates both secondary metabolism and morphologic differentiation in Streptomyces avermitilis ATCC 31272. Curr Microbiol 53:204–208
76. Ramos JL, Martinez-Bueno M, Molina-Henares AJ, Teran W, Watanabe K, Zhang X, Gallegos MT, Brennan R, Tobes R (2005) The TetR family of transcriptional repressors. Microbiol Mol Biol Rev 69:326–356
77. Reading C, Cole M (1977) Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother 11:852–857
78. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. doi:10.1093/nar/gkv007
79. Rodriguez-Garcia A, Barreiro C, Santos-Beneit F, Sola-Landa A, Martin JF (2007) Genome-wide transcriptomic and proteomic analysis of the primary response to phosphate limitation in Streptomyces coelicolor M145 and in a Delta-phoP mutant. Proteomics 7:2410–2429
80. Salehghamari E, Hamedi J, Elahi E, Sepehrizadeh Z, Sadeghi M, Muth G (2012) Prediction of the pho regulon in Streptomyces clavuligerus DSM 738. New Microbiol 35:447–457
81. Sanchez L, Brana AF (1996) Cell density influences antibiotic biosynthesis in Streptomyces clavuligerus. Microbiology 142(Pt 5):1209–1220
82. Santamarta I, Lopez-Garcia MT, Kurt A, Nardiz N, Alvarez-Alvarez R, Perez-Redondo R, Martin JF, Liras P (2011) Characterization of DNA-binding sequences for CcaR in the cephamycin-clavulanic acid supercluster of Streptomyces clavuligerus. Mol Microbiol 81:968–981
83. Santamarta I, Rodriguez-Garcia A, Perez-Redondo R, Martin JF, Liras P (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
84. Santos-Beneit F, Rodriguez-Garcia A, Sola-Landa A, Martin JF (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
85. Sevcikova B, Benada O, Kofronova O, Kormanec J (2001) Stress-response sigma factor (sigma H) is essential for morphological differentiation of Streptomyces coelicolor A3(2). Arch Microbiol 177:98–106
86. Sevcikova B, Rezuchova B, Homerova D, Kormanec J (2010) The anti–anti-sigma factor BldG is involved in activation of the stress response sigma factor (sigma H) in Streptomyces coelicolor A3(2). J Bacteriol 192:5674–5681
87. Shiina T, Tanaka K, Takahashi H (1991) Sequence of hrdB, an essential gene encoding sigma-like transcription factor of Streptomyces coelicolor A3(2): homology to principal sigma factors. Gene 107:145–148
88. Smyth GK (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3(article 3). doi:10.2202/1544-6115.1027
89. Sola-Landa A, Moura RS, Martin JF (2003) The two-component PhoR–PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proc Natl Acad Sci USA 100:6133–6138
90. Sola-Landa A, Rodriguez-Garcia A, Franco-Dominguez E, Martin JF (2005) Binding of PhoP to promoters of phosphate-regulated genes in Streptomyces coelicolor: identification of PHO boxes. Mol Microbiol 56:1373–1385
91. Song JY, Jensen SE, Lee KJ (2010) Clavulanic acid biosynthesis and genetic manipulation for its overproduction. Appl Microbiol Biotechnol 88:659–669
92. Song JY, Jeong H, Yu DS, Fischbach MA, Park HS, Kim JJ, Seo JS, Jensen SE, Oh TK, Lee KJ, Kim JF (2010) Draft genome sequence of Streptomyces clavuligerus NRRL 3585, a producer of diverse secondary metabolites. J Bacteriol 192:6317–6318
93. Tahlan K, Anders C, Jensen SE (2004) The paralogous pairs of genes involved in clavulanic acid and clavam metabolite biosynthesis are differently regulated in Streptomyces clavuligerus. J Bacteriol 186:6286–6297
94. Tahlan K, Park HU, Jensen SE (2004) Three unlinked gene clusters are involved in clavam metabolite biosynthesis in Streptomyces clavuligerus. Can J Microbiol 50:803–810
95. Takano E, Tao M, Long F, Bibb MJ, Wang L, Li W, Buttner MJ, Bibb MJ, Deng ZX, Chater KF (2003) A rare leucine codon in adpA is implicated in the morphological defect of bldA mutants of Streptomyces coelicolor. Mol Microbiol 50:475–486
96. Takano H, Fujimoto M, Urano H, Beppu T, Ueda K (2011) Cross-interaction of anti-sigmaH factor RshA with BldG, an anti-sigma factor antagonist in Streptomyces griseus. FEMS Microbiol Lett 314:158–163. doi:10.1111/j.1574-6968.2010.02155.x
97. Trepanier NK, Jensen SE, Alexander DC, Leskiw BK (2002) The positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus is mistranslated in a bldA mutant. Microbiology 148:643–656
98. Tzanis A, Dalton KA, Hesketh A, den Hengst CD, Buttner MJ, Thibessard A, Kelemen GH (2014) A sporulation-specific, sigF-dependent protein, SspA, affects septum positioning in Streptomyces coelicolor. Mol Microbiol 91:363–380
99. Uguru GC, Stephens KE, Stead JA, Towle JE, Baumberg S, McDowall KJ (2005) Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol Microbiol 58:131–150
100. Urabe H, Aoyagi N, Ogawara H, Motojima K (2008) Expression and characterization of the Streptomyces coelicolor serine/threonine protein kinase PkaD. Biosci Biotechnol Biochem 72:778–785
101. van Wezel GP, McDowall KJ (2011) The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep 28:1311–1333
102. van Wezel GP, van der Meulen J, Kawamoto S, Luiten RG, Koerten HK, Kraal B (2000) ssgA is essential for sporulation of Streptomyces coelicolor A3(2) and affects hyphal development by stimulating septum formation. J Bacteriol 182:5653–5662
103. Viollier PH, Kelemen GH, Dale GE, Nguyen KT, Buttner MJ, Thompson CJ (2003) Specialized osmotic stress response systems involve multiple SigB-like sigma factors in Streptomyces coelicolor. Mol Microbiol 47:699–714
104. Ward JM, Hodgson JE (1993) The biosynthetic genes for clavulanic acid and cephamycin production occur as a ‘super-cluster’ in three Streptomyces. FEMS Microbiol Lett 110:239–242
105. Wright F, Bibb MJ (1992) Codon usage in the G + C-rich Streptomyces genome. Gene 113:55–65
106. Xu W, Huang J, Cohen SN (2008) Autoregulation of AbsB (RNase III) expression in Streptomyces coelicolor by endoribonucleolytic cleavage of absB operon transcripts. J Bacteriol 190:5526–5530
107. Yamazaki H, Ohnishi Y, Horinouchi S (2000) An A-factor-dependent extracytoplasmic function sigma factor (AdsA) that is essential for morphological development in Streptomyces griseus. J Bacteriol 182:4596–4605
108. Yamazaki H, Ohnishi Y, Horinouchi S (2003) Transcriptional switch on of ssgA by A-factor, which is essential for spore septum formation in Streptomyces griseus. J Bacteriol 185:1273–1283
109. Zaburannyy N, Ostash B, Fedorenko V (2009) TTA Lynx: a web-based service for analysis of actinomycete genes containing rare TTA codon. Bioinformatics 25:2432–2433