May 25, 2011 - 78 S. L. Otten, C. Olano and C. R. Hutchinson, Microbiology, 2000, ..... 273 A. J. Woo, J. S. Dods, E. Susanto, D. Ulgiati and L. J. Abraham,. Mol.
C
View Online
NPR
Dynamic Article Links
150 transcriptional units. These included many genes that had previously been identified as having critical roles in the regulation of development or secondary metabolism or both. In addition, BldD was revealed to target genes associated with branched-chain amino acid biosynthesis, polysaccharide metabolism, production of cyclic-di-GMP (a secondary messenger involved in bacterial development) and some regulated by other bld genes.268 There is no doubt that the study by ChIP-based methods of additional regulatory genes will produce yet more step-changes in our understanding of gene regulation, the coordination of antibiotic production with development, and links to primary metabolism. In turn, this new knowledge may reveal additional strategies for expanding the screening of streptomycetes for new antibiotics. One of the members of the BldD regulon is bldA, which encodes the tRNA for the leucine codon UUA.269 This codon is not found in genes essential for vegetative growth, but in around 150 that are primarily associated with morphological development and secondary metabolism.270 The latter include the CSR genes actII-ORF4 and redZ, as well as the pleiotropic regulator adpA (bldH). Although the identification of a link to these three regulatory genes may be sufficient to explain why production of antibiotics, as well as spores, is blocked by the disruption of BldD, it is possible that other genes under the control of the BldD regulon contribute significantly to antibiotic production and morphological development. Previously identified regulatory genes also provide points from which to investigate regulation that occurs upstream of their action. The exemplar of this approach is the study of the regulation of streptomycin production in S. griseus. Starting from Nat. Prod. Rep., 2011, 28, 1311–1333 | 1325
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
View Online
StrR (the URAP) an ungapped pathway was traced back to synthesis of A-factor (Fig. 1). This landmark work was relatively labour intensive and time consuming, requiring the purification of DNA-binding activities in conjunction with their repeated assay. However, more recently, techniques have been developed that circumvent the need for extensive purification, for example, by using ‘chips’ derivatized with probes that can capture, from crude extracts, binding proteins that are identified in a second step by mass spectrometry,271,272 by employing estimates of the pI and mass of an interacting protein to facilitate the identification of candidate spots on a standard 2D gels,273 or by exploiting the change in the gel mobility of a protein when it binds to DNA.274,275 All of these techniques can be applied directly to the study of streptomycetes. Another approach with great promise is ‘DNA sampling’, which allows the rapid isolation of specific DNA fragments, together with attached proteins, directly from cells.276 Application of this elegant and powerful technique to streptomycetes will, however, require the construction of suitable strains and plasmid vectors. Genes known to regulate the production of antibiotics in streptomycetes are summarised in Table 1. Transcriptomics is producing genome-wide views of the changes in gene expression that occur during growth and development,277,278 in response to stimuli277,279 and as the result of gene disruption.29,138,150,277,280–283 It has revealed, for example, that disruption of a CSR can influence expression of others and the pleiotropic regulator afsS (afsR2), suggesting that CSRs are not strictly pathway specific and can feedback on earlier regulatory steps, respectively.29 Not all genes that have altered expression as the result of disrupting a regulatory gene are necessarily direct targets. Indeed most of the genes with altered expression resulting from disruption of bldD (described above) were found, using ChIP-chip in the same study, not to be bound by this transcription factor in vivo.268 Thus, knowledge of sequences recognised by a regulatory gene is required in order to discriminate direct from indirect effects on gene expression. In cases where several sites of binding have been identified, it is possible to align the corresponding sequences to produce a position weight matrix (PWM) that can be used to screen a genome(s) for similar sites. This bioinformatic approach provided considerable insight into the role of DasR.55 Where there are insufficient or no known natural binding sites to produce a robust PWM, the sequences recognised by a DNAbinding protein can be determined using SELEX (selective enrichment of ligands by exponential enrichment) provided the protein can be purified in a soluble form. This experimental approach has been applied to AtrA.43 The resulting PWM identified the two known binding sites in the promoter of actII-ORF4 as well as several others that have now been verified (K. J. McDowall, unpublished data). With a robotic setup the selections can be done in less than a day. Bioinformatic, PWM-based screens are also a valuable addition to ChIP-based experiments, as the latter can fail to detect bona fide binding sites (i.e. produce false negatives). A review covering both ChIP-based approaches and DNA sampling has recently been published.284 Proteomics, although unable, at least currently, to provide the same level of gene coverage as transcriptomics, promises to continue to contribute to our understanding of gene regulation in streptomycetes. It has revealed recently, for example, that in 1326 | Nat. Prod. Rep., 2011, 28, 1311–1333
liquid culture S. coelicolor undergoes a complex early differentiation process (which includes antibiotic production, but not sporulation) broadly comparable to that which occurs on solid media,285 and that primary and secondary metabolism (as measured using ‘solid’ cultures) tend to be divided between the vegetative mycelium and aerial hyphae, respectively.286 Proteomics is also being used to discover natural products and their biosynthetic pathways via screening that exploits characteristics of the synthetases for non-ribosomal peptides and the synthases for polyketides,287 as well as to study the consequences of individual mutations (for examples, see refs 138, 282, 288–290). For details relating to the technical aspects of proteomics, the reader is directed to reviews by others.291–294 A challenge for the next decade will be to integrate data from transcriptomics and proteomics with information from other omics approaches, such as metabolomics, to produce mathematical models that describe streptomycetes not only as homoeostatic systems, but as systems that differentiate.295 Progress is being made132,296 and shows promise in revealing how metabolism can be engineered to increase production of natural products (for reviews, see refs 297, 298). Strains are being engineered to supply increased levels of precursors for particular classes of secondary metabolites in the hope of producing hosts that will enable the heterologous production of cryptic antibiotics to levels that allow the characterisation of their activity and, later, to produce enough for pre-clinical and clinical testing.299
11 Conclusions and future perspectives Study of the regulation of antibiotic production in streptomycetes has revealed, and will continue to reveal, new strategies for ‘awakening’ production of antibiotics, thereby allowing us to tap more effectively the rich stores of natural products encoded in the genomes of streptomycetes. The discovery of new antimicrobials is critically important given the alarming rate at which resistance to existing antibiotics is emerging in pathogens, and the lack of effective antimicrobials emerging from alternative and much vaunted approaches, such as phage therapy.300 The recent discovery of an adaptive immune system in bacteria has important ramifications for the effectiveness of phage therapy.301,302 Adoption of genome-wide approaches, the ‘omics’, will undoubtedly make an important contribution to a systems-level understanding of streptomycetes. Furthermore, it also not unreasonable to assume that this new knowledge will reveal further means by which gene regulation can be manipulated to stimulate expression of antibiotic clusters that would otherwise be cryptic in laboratory screens. In terms of increasing production of secondary metabolites to commercial scales once their clinical value has been established, strain improvement programmes will continue to utilise genetic screens, such as the one described earlier (Section 3.1) that was based on isolating mutations in RNA polymerase or ribosomal protein S12. Genetic screens should also benefit enormously from our ability to recombine mutations isolated from different lines of strain improvement using genome shuffling.303 Nonetheless, directed engineering still has the potential to make a significant contribution, as illustrated by the increased levels of tylosin produced when CSRs were overproduced in strains that were the products of intensive, empirical improvement programmes.104 This journal is ª The Royal Society of Chemistry 2011
View Online
Table 1 Streptomyces genes that regulate production of antibiotics
Gene
ID
Known or likely function(s) of gene product(s)
Refs
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
Regulators with ungapped links that extend beyond antibiotic gene clusters strR
SGR5931
adpA
SGR4742
arpA
SGR3731
afsA
SGR6889
arfA
SCO3841
actII-ORF4
SCO5085
redD
SCO5877
dasR
SCO5231
atrA
SCO4118
rok7B7
SCO6008
absA1/2
SCO3225/3226
SCO0608 SCO6808 redZ
SCO5881
cpkO
SCO6280
scbR
SCO6265
scbA
SCO6266
ndgR
SCO5552
relA
SCO1513
rshA relC
SCO5794 SCO4648
rpoB
SCO4654
cprA cprB
SCO6071 SCO6312
SCO3201
SCO3201
Ultimate (final) regulator of the streptomycin cluster in S. griseus; transcriptional activator Activator of strR; S. coelicolor homologue is BldH; member of AraC/XylS family Transcriptional repressor of adpA; receptor for A factor, which blocks DNA-binding activity Catalyses committal step in synthesis of A factor; S. coelicolor homologue is ScbA Binds to promoters of adpA (bldH) in both S. griseus and S. lividans; evolutionarily conserved; disruption reduces level of undecylprodigiosin (RED) produced in S. lividans; lacks an obvious DNA-binding domain Ultimate activator of the ACT (act) biosynthetic cluster in S. coelicolor and S. lividans; SARP family regulator Ultimate activator of the RED (red) biosynthetic cluster in S. coelicolor and S. lividans; SARP family regulator Transcriptional repressor of actII-ORF4; receptor for GlcN-6-P, which blocks DNA-binding activity; master regulator of genes involved in chitin catabolism; links to development; regulator of scbA (see below) Transcriptional activator of actII-ORF4; member of TetR family; transduced signal is unknown; homologue of AveI in S. avermitilis; conditional regulator of S. griseus strR; activator of nagE2 Transcriptional activator of actII-ORF4; regulator of xylose metabolism; regulon overlaps that of DasR Two component system; located in calcium-dependent antibiotic (CDA) cluster; negatively regulates CDA production, regulation appears independent of CdaR; AbsA2 binds to actII-ORF4 increasing Act production; transduced signal is unknown; reported to bind to promoter of redD Binds to the promoters of actII-ORF4 and redD; negative regulator of antibiotic production and sporulation in S. coelicolor Binds to the promoters of actII-ORF4 and redD; negative regulator of antibiotic production and sporulation in S. coelicolor Orphan response regulator; transcriptional activator of redD; TTA codon in gene explains bldA dependence of RED production Ultimate activator of the cryptic polyketide (CPK) cluster in S. coelicolor; gene also called kasO Transcriptional repressor of cpkO; DNA-binding activity blocked by g-butyrolactones; autoregulates own expression; located within cpk cluster; impacts ACT production Catalyses committal step in synthesis of S. coelicolor g-butyrolactones; S. griseus homologue is afsA; transcription activated by ScbR; located within cpk cluster; impacts ACT production Binds to the promoter of scbR; controls leucine biosynthesis; activity dependent on nitrogen; widely conserved in streptomycetes; member of IclR family; homologue regulates doxorubicin in S. peucetius Under limited amino acids or glucose, catalyses synthesis of (p)ppGpp, which binds RNA polymerase and signals start of stringent response; essential for antibiotic production in S. coelicolor and other species Catalyses (p)ppGpp synthesis under conditions of limited phosphate Also called RplK; specific mutation impairs production of (p)ppGpp and ACT in S. coelicolor; confirmed in other species Subunit of RNA polymerase; mutants that confer rifampicin resistance confer stringent response-like characteristics Encodes ArpA homologue that activates antibiotic production. Encodes ArpA homologue that is 91% identical to CprA, but represses antibiotic production. TetR homologue; represses antibiotic production when placed on multi-copy vector; no clear phenotype for deletion mutant.
31 33 34, 35 40 45 30 304, 305 47, 54, 201 42, 43, 201, 306 203, 204 46, 48, 50, 307
308 308 74 255 249 249 256 117, 124, 309 120, 124 310–312 127, 313 314 314 315
Regulators in pathways with missing link to antibiotic gene clusters afsS
SCO4425
afsR
SCO4426
afsK kbpA pkaG & afsL
SCO4423 SCO4422 SCO4487, SCO4377
Also called AfsR2; similar to sigma factors; overexpression stimulates antibiotic production in several species; regulator of nutrient stress responses Similar to SARPs; activates transcription of afsS; DNA-binding activity blocked by phosphorylation Major serine/threonine kinase that phosphorylates AfsR; shown to bind AdoMet Modulates ability of AfsK to phosphorylate AfsR Two AfsR-like kinases that also phosphorylate AfsR
This journal is ª The Royal Society of Chemistry 2011
143, 144, 147, 150 146, 148, 163 153, 316, 317 155 154, 163
Nat. Prod. Rep., 2011, 28, 1311–1333 | 1327
View Online
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
Table 1 (Contd. )
Gene
ID
phoRP
SCO4229, SCO4230
bld
Various
dmdR1/adm
SCO4394
facC
AF103943
sigQ
SCO4908
afsQ1/2
SCO4907/6
Known or likely function(s) of gene product(s)
Refs
Two component system that regulates uptake and assimilation of phosphate; perturbation of system stimulates antibiotic production in S. coelicolor and S. lividans; PhoP binds promoter of AfsS probably blocking activation by AfsR; PhoP also binds promoter of glnR, a major regulator of nitrogen assimilation Several regulatory proteins required for the development of aerial hyphae from the previously ‘bald’ vegetative mycelium, as well as for production of antibiotics Regulators of iron metabolism; adm overlaps dmdR1 on the opposite strand; disruption of adm increases production of ACT and RED Factor C; secreted signalling protein that stimulates sporulation and has a link to A-factor production; extracellular Factor C induces submerged sporulation and streptomycin production in S. griseus Putative sigma factor; disruption enhances antibiotic production and delays sporulation in S. coelicolor Two-component system; stimulates antibiotic production in S. lividans; conditionally required for normal levels of antibiotic production and morphological development in S. coelicolor; regulates expression of sigQ
139, 141, 318–320
17, 20, 321, 322 183, 184 260–263 323 323, 324
Orphan regulators and cluster-situated regulators (present at least in S. coelicolor) absB
SCO5572
absC
SCO5405
absR1/2
SCO6992/3
cdgA
SCO2817
cutRS earE1/2
SCO5862/3 SCO6421/2
eshA
SCO7699
nsdA
SCO5582
nsdB
SCO7252
rapA1/2
SCO5403/4
rrdA
SCO1104
ssgA
SCO3926
wblA
SCO3579 SCO1712
cdaR mmyB
SCO3217 CAC36754
mmfR
CAC36768
Endoribonuclease III, essential for antibiotic production in S. coelicolor; autoregulates own production; cleaves mRNA of adpA; disruption affects, but does not block sporulation process Required for production of ACT and RED in S. coelicolor under conditions of limited zinc; directly represses gene cluster of coelibactin, a non-ribosomally synthesized peptide predicted to have siderophore-like activity; no obvious effect on morphological development Essential for antibiotic production in S. coelicolor; no obvious effect on morphological development; located close to absA diguanylate cyclase; enhanced expression blocks development and ACT production in S. coelicolor; regulated directly by BldD TCS reported to repress ACT production in S. lividans Two-component system in S. coelicolor; located close to red cluster; disruption reduces level of RED produced Required for antibiotic production in S. coelicolor and normal development in S. griseus; accentuates (p)ppGpp accumulation; possible nucleotide-binding protein Negative regulator of antibiotic production and development in several streptomycetes; target of BldD regulation Negative regulator of antibiotic production and development in several streptomycetes; transcribed divergently from gene of an Aph-like antibiotic phosphotransferase protein; contains a tetratricopeptide repeat domain TCS; disruption reduces production of ACT and cryptic polyketide in S. coelicolor; appears to function via the corresponding URAPs; transduced signal is unknown TetR family member; negatively regulates expression of redD (not yet known whether direct or indirect); impacts ACT production perhaps as a result of sharing precursors with RED Cell division activator with pleiotropic effect on development; strongly enhances RED production and blocks production of ACT. WhiB-like transcription factor; disruption strongly increases antibiotic production in S. coelicolor; probably functions similarly in most, if not all, streptomycetes Transcriptional regulator that modulates antibiotic production in S. coelicolor; member of TetR family CSR of the calcium-dependent antibiotic (cda) cluster URAP (transcriptional activator) of the methylenomycin (Mm) cluster on the SCP1 plasmid Member of ArpA family; receptor for novel furans (related to g-butyrolactones) that autoregulate Mm production; functions in concert with MmyR; represses Mm and furan production until autoregulator accumulates
Looking ahead, next-generation sequencing and now also single molecule sequencing, which allow almost complete genome sequences to be obtained in a matter of weeks or even days will revolutionise the field. With prices dropping below the £400 mark per genome, it is feasible to sequence an entire strain collection. With around 20 secondary metabolite clusters in a single actinomycete, it is easy to envisage how sequencing will 1328 | Nat. Prod. Rep., 2011, 28, 1311–1333
325–327 180
328 268 329 330 330 268, 331, 332 333 334 335 233 336, 337
307 82 82, 257
yield the genetic maps of tens if not hundreds of thousands of secondary metabolite gene clusters. Therefore, the rate-limiting (and most costly) step has now become data analysis. And while such huge numbers of new clusters are certainly informative, it is not a guarantee for the discovery of truly novel products that will aid us in the fight against multi-drug resistant pathogens. After all, the biosynthetic gene clusters of a truly novel class of This journal is ª The Royal Society of Chemistry 2011
View Online
secondary metabolites will share little, if any, similarity with those of trademark antibiotics. However, with increasing understanding of how antibiotic production is controlled in the producing organisms, we will most likely be able to stimulate production of new activities that may well stem from truly novel classes of secondary metabolites. This is a major challenge for the years to come.
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
12 Acknowledgements We thank our colleagues in the Streptomyces community for sharing unpublished results and ideas, and providing constructive comments. We especially appreciated the thoughtful input of David Hopwood and Richard Baltz.
13 References 1 K. Shiomi and S. Omura, Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2004, 80, 245–258. 2 P. Caffrey, J. F. Aparicio, F. Malpartida and S. B. Zotchev, Curr. Top. Med. Chem., 2008, 8, 639–653. 3 R. H. Baltz, Curr. Opin. Pharmacol., 2008, 8, 557–563. 4 E. I. Graziani, Nat. Prod. Rep., 2009, 26, 602–609. 5 C. Olano, C. Mendez and J. A. Salas, Mar. Drugs, 2009, 7, 210–248. 6 C. Olano, C. Mendez and J. A. Salas, Nat. Prod. Rep., 2009, 26, 628– 660. 7 J. Davies, Curr. Opin. Chem. Biol., 2011, 15, 5–10. 8 G. L. Challis and D. A. Hopwood, Proc. Natl. Acad. Sci. U. S. A., 2003, 100, 14555–14561. 9 J. Berdy, J. Antibiot., 2005, 58, 1–26. 10 D. A. Hopwood, Microbiology, 1999, 145, 2183–2202. 11 D. A. Hopwood, Science, 2003, 301, 1850–1851. 12 J. M. Willey and A. A. Gaskell, Chem. Rev., 2011, 111, 174–187. 13 K. F. Chater, S. Biro, K. J. Lee, T. Palmer and H. Schrempf, FEMS Microbiol. Rev., 2010, 34, 171–198. 14 M. Kaltenpoth, Trends Microbiol., 2009, 17, 529–535. 15 R. Loria, J. Coombs, M. Yoshida, J. Kers and R. Bukhalid, Physiol. Mol. Plant Pathol., 2003, 62, 65–72. 16 R. Loria, J. Kers and M. Joshi, Annu. Rev. Phytopathol., 2006, 44, 469–487. 17 K. F. Chater, Philos. Trans. R. Soc. London, Ser. B, 2006, 361, 761– 768. 18 K. F. Chater and G. Chandra, FEMS Microbiol. Rev., 2006, 30, 651– 672. 19 D. Claessen, W. de Jong, L. Dijkhuizen and H. A. B. Wosten, Trends Microbiol., 2006, 14, 313–319. 20 K. Flardh and M. J. Buttner, Nat. Rev. Microbiol., 2009, 7, 36–49. 21 S. Horinouchi, Biosci., Biotechnol., Biochem., 2007, 71, 283–299. 22 S. Horinouchi and T. Beppu, Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2007, 83, 277–295. 23 G. P. van Wezel and E. Vijgenboom, in Advances in Applied Microbiology, Vol. 56, 2004, pp. 65–88. 24 A. Manteca, M. Fernandez and J. Sanchez, Microbiology, 2005, 151, 3689–3697. 25 A. Manteca and J. Sanchez, Appl. Environ. Microbiol., 2009, 75, 2920–2924. 26 C. Corre and G. L. Challis, Nat. Prod. Rep., 2009, 26, 977–986. 27 H. Gross, Curr. Opin. Drug Discovery Dev., 2009, 12, 207–219. 28 M. Nett, H. Ikeda and B. S. Moore, Nat. Prod. Rep., 2009, 26, 1362– 1384. 29 J. Huang, J. Shi, V. Molle, B. Sohlberg, D. Weaver, M. J. Bibb, N. Karoonuthaisiri, C. J. Lih, C. M. Kao, M. J. Buttner and S. N. Cohen, Mol. Microbiol., 2005, 58, 1276–1287. 30 H. C. Gramajo, E. Takano and M. J. Bibb, Mol. Microbiol., 1993, 7, 837–845. 31 D. Vujaklija, S. Horinouchi and T. Beppu, J. Bacteriol., 1993, 175, 2652–2661. 32 A. Tomono, Y. Tsai, H. Yamazaki, Y. Ohnishi and S. Horinouchi, J. Bacteriol., 2005, 187, 5595–5604. 33 Y. Ohnishi, S. Kameyama, H. Onaka and S. Horinouchi, Mol. Microbiol., 1999, 34, 102–111.
This journal is ª The Royal Society of Chemistry 2011
34 H. Onaka, N. Ando, T. Nihira, Y. Yamada, T. Beppu and S. Horinouchi, J. Bacteriol., 1995, 177, 6083–6092. 35 H. Onaka and S. Horinouchi, Mol. Microbiol., 1997, 24, 991–1000. 36 T. Higashi, Y. Iwasaki, Y. Ohnishi and S. Horinouchi, J. Bacteriol., 2007, 189, 3515–3524. 37 Y. Ohnishi, H. Yamazaki, J. Y. Kato, A. Tomono and S. Horinouchi, Biosci., Biotechnol., Biochem., 2005, 69, 431–439. 38 G. Akanuma, H. Hara, Y. Ohnishi and S. Horinouchi, Mol. Microbiol., 2009, 73, 898–912. 39 S. Horinouchi, Front. Biosci., 2002, 7, D2045–D2057. 40 J. Y. Kato, N. Funa, H. Watanabe, Y. Ohnishi and S. Horinouchi, Proc. Natl. Acad. Sci. U. S. A., 2007, 104, 2378–2383. 41 B. Hong, S. Phornphisutthimas, E. Tilley, S. Baumberg and K. J. McDowall, Biotechnol. Lett., 2007, 29, 57–64. 42 S. Hirano, K. Tanaka, Y. Ohnishi and S. Horinouchi, Microbiology, 2008, 154, 905–914. 43 G. C. Uguru, K. E. Stephens, J. A. Stead, J. E. Towle, S. Baumberg and K. J. McDowall, Mol. Microbiol., 2005, 58, 131–150. 44 A. Martinez-Antonio and J. Collado-Vides, Curr. Opin. Microbiol., 2003, 6, 482–489. 45 D. Xu, T. J. Kim, Z. Y. Park, S. K. Lee, S. H. Yang, H. J. Kwon and J. W. Suh, Biochem. Biophys. Res. Commun., 2009, 379, 319–323. 46 N. L. McKenzie and J. R. Nodwell, J. Bacteriol., 2007, 189, 5284– 5292. 47 S. Rigali, F. Titgemeyer, S. Barends, S. Mulder, A. W. Thomae, D. A. Hopwood and G. P. van Wezel, EMBO Rep., 2008, 9, 670– 675. 48 N. L. Sheeler, S. V. MacMillan and J. R. Nodwell, J. Bacteriol., 2005, 187, 687–696. 49 P. Brian, F. J. Riggle, R. A. Santos and W. C. Champness, J. Bacteriol., 1996, 178, 3221–3231. 50 T. B. Anderson, P. Brian and W. C. Champness, Mol. Microbiol., 2001, 39, 553–566. 51 W. Champness, P. Riggle, T. Adamidis and P. Vandervere, in 8th International Symp on Biology of Actinomycetes (ISBA-8), Madison, WI, 1991, pp. 55–60. 52 N. L. McKenzie, M. Thaker, K. Koteva, D. W. Hughes, G. D. Wright and J. R. Nodwell, J. Antibiot., 2010, 63, 177–182. 53 M. Bierman, R. Logan, K. Obrien, E. T. Seno, R. N. Rao and B. E. Schoner, Gene, 1992, 116, 43–49. 54 S. Rigali, H. Nothaft, E. E. E. Noens, M. Schlicht, S. Colson, M. Muller, B. Joris, H. K. Koerten, D. A. Hopwood, F. Titgemeyer and G. P. van Wezel, Mol. Microbiol., 2006, 61, 1237–1251. 55 S. Colson, J. Stephan, T. Hertrich, A. Saito, G. P. van Wezel, F. Titgemeyer and S. Rigali, J. Mol. Microbiol. Biotechnol., 2007, 12, 60–66. 56 J. E. Towle, PhD Thesis, University of Leeds, 2007. 57 B. Boomsma, MSc Thesis, University of Leiden, 2009. 58 I. Borodina, J. Siebring, J. Zhang, C. P. Smith, G. van Keulen, L. Dijkhuizen and J. Nielsen, J. Biol. Chem., 2008, 283, 25186– 25199. 59 B. Ruiz, A. Chavez, A. Forero, Y. Garcia-Huante, A. Romero, M. Sanchez, D. Rocha, B. Sanchez, R. Rodriguez-Sanoja, S. Sanchez and E. Langley, Crit. Rev. Microbiol., 2010, 36, 146–167. 60 J. Thykaer and J. Nielsen, Metab. Eng., 2003, 5, 56–69. 61 G. Stephanopoulos, AIChE J., 2002, 48, 920–926. 62 L. Heide, B. Gust, C. Anderle and S. M. Li, Curr. Top. Med. Chem., 2008, 8, 667–679. 63 N. Bate, G. Stratigopoulos and E. Cundliffe, Mol. Microbiol., 2002, 43, 449–458. 64 D. R. D. Bignell, N. Bate and E. Cundliffe, Mol. Microbiol., 2007, 63, 838–847. 65 G. Stratigopoulos, A. R. Gandecha and E. Cundliffe, Mol. Microbiol., 2002, 45, 735–744. 66 E. Cundliffe, in Annual Meeting of the Society for Industrial Microbiology, Chicago, IL, 2005, pp. 500–506. 67 E. Cundliffe, J. Microbiol. Biotechnol., 2008, 18, 1485–1491. 68 F. Karray, E. Darbon, C. N. Hoang, J. Gagnat and J. L. Pernodet, J. Bacteriol., 2010, 192, 5813–5821. 69 K. Q. Yang, L. Han and L. C. Vining, J. Bacteriol., 1995, 177, 6111– 6117. 70 K. Q. Yang, L. Han, J. Y. He, L. R. Wang and L. C. Vining, Gene, 2001, 279, 165–173. 71 L. Wang and L. C. Vining, Microbiology, 2003, 149, 1991–2004.
Nat. Prod. Rep., 2011, 28, 1311–1333 | 1329
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
View Online
72 L. Q. Wang, X. Y. Tian, J. Wang, H. H. Yang, K. Q. Fan, G. M. Xu, K. Q. Yang and H. R. Tan, Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 8617–8622. 73 J. White and M. Bibb, J. Bacteriol., 1997, 179, 627–633. 74 E. P. Guthrie, C. S. Flaxman, J. White, D. A. Hodgson, M. J. Bibb and K. F. Chater, Microbiology, 1998, 144, 2007–2007. 75 E. Takano, H. C. Gramajo, E. Strauch, N. Andres, J. White and M. J. Bibb, Mol. Microbiol., 1992, 6, 2797–2804. 76 K. J. Stutzman-Engwall, S. L. Otten and C. R. Hutchinson, J. Bacteriol., 1992, 174, 144–154. 77 K. Furuya and C. R. Hutchinson, J. Bacteriol., 1996, 178, 6310– 6318. 78 S. L. Otten, C. Olano and C. R. Hutchinson, Microbiology, 2000, 146, 1457–1468. 79 S. K. Ahn, K. Tahlan, Z. Yu and J. Nodwell, J. Bacteriol., 2007, 189, 6655–6664. 80 A. R. Willems, K. Tahlan, T. Taguchi, K. Zhang, Z. Z. Lee, K. Ichinose, M. S. Junop and J. R. Nodwell, J. Mol. Biol., 2008, 376, 1377–1387. 81 T. B. K. Le, H. P. Fiedler, C. D. den Hengst, S. K. Ahn, A. Maxwell and M. J. Buttner, Mol. Microbiol., 2009, 72, 1462–1474. 82 S. O’Rourke, A. Wietzorrek, K. Fowler, C. Corre, G. L. Challis and K. F. Chater, Mol. Microbiol., 2009, 71, 763–778. 83 J. D. Helmann, Adv. Microb. Physiol., 2002, 46, 47–110. 84 L. C. Foulston and M. J. Bibb, Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 13461–13466. 85 J. M. Willey and W. A. van der Donk, Annu. Rev. Microbiol., 2007, 61, 477–501. 86 A. Staron, H. J. Sofia, S. Dietrich, L. E. Ulrich, H. Liesegang and T. Mascher, Mol. Microbiol., 2009, 74, 557–581. 87 B. E. Brooks and S. K. Buchanan, Biochim. Biophys. Acta, Biomembr., 2008, 1778, 1930–1945. 88 G. P. van Wezel, J. White, G. Hoogvliet and M. J. Bibb, J. Mol. Microbiol. Biotechnol., 2000, 2, 551–556. 89 A. Wietzorrek and M. Bibb, Mol. Microbiol., 1997, 25, 1181–1184. 90 P. J. Sheldon, S. B. Busarow and C. R. Hutchinson, Mol. Microbiol., 2002, 44, 449–460. 91 F. Lombo, A. F. Brana, C. Mendez and J. A. Salas, J. Bacteriol., 1999, 181, 642–647. 92 L. Tang, A. Grimm, Y. X. Zhang and C. R. Hutchinson, Mol. Microbiol., 1996, 22, 801–813. 93 K. J. McDowall, A. Thamchaipenet and I. S. Hunter, J. Bacteriol., 1999, 181, 3025–3032. 94 M. Rodriguez, L. E. Nunez, A. F. Brana, C. Mendez, J. A. Salas and G. Blanco, Mol. Microbiol., 2008, 69, 633–645. 95 Y. Chen, E. Wendt-Pienkowski and B. Shen, J. Bacteriol., 2008, 190, 5587–5596. 96 W. Boos and A. Bohm, Trends Genet., 2000, 16, 404–409. 97 D. J. Wilson, Y. Q. Xue, K. A. Reynolds and D. H. Sherman, J. Bacteriol., 2001, 183, 3468–3475. 98 I. Molnar, J. F. Aparicio, S. F. Haydock, L. E. Khaw, T. Schwecke, A. Konig, J. Staunton and P. F. Leadlay, Gene, 1996, 169, 1–7. 99 T. Brautaset, O. N. Sekurova, H. Sletta, T. E. Ellingsen, A. R. Strom, S. Valla and S. B. Zotchev, Chem. Biol., 2000, 7, 395–403. 100 V. Schreiber, C. Steegborn, T. Clausen, W. Boos and E. Richet, Mol. Microbiol., 2000, 35, 765–776. 101 K. Gerdes, M. Howard and F. Szardenings, Cell, 141, 927– 942. 102 N. Bate, D. R. D. Bignell and E. Cundliffe, Mol. Microbiol., 2006, 62, 148–156. 103 A. S. Eustaquio, S. M. Li and L. Heide, Microbiology, 2005, 151, 1949–1961. 104 G. Stratigopoulos, N. Bate and E. Cundliffe, Mol. Microbiol., 2004, 54, 1326–1334. 105 M. J. Smanski, R. M. Peterson, S. R. Rajski and B. Shen, Antimicrob. Agents Chemother., 2009, 53, 1299–1304. 106 B. Gust, G. Chandra, D. Jakimowicz, Y. Q. Tian, C. J. Bruton and K. F. Chater, in Advances in Applied Microbiology, Vol. 54, 2004, pp. 107–128. 107 E. Strauch, E. Takano, H. A. Baylis and M. J. Bibb, Mol. Microbiol., 1991, 5, 289–298. 108 V. Jain, M. Kumar and D. Chatterji, J. Microbiol., 2006, 44, 1–10. 109 D. Chatterji and A. K. Ojha, Curr. Opin. Microbiol., 2001, 4, 160– 165.
1330 | Nat. Prod. Rep., 2011, 28, 1311–1333
110 H. P. Godfrey, J. V. Bugrysheva and F. C. Cabello, Trends Microbiol., 2002, 10, 349–351. 111 K. Potrykus and M. Cashel, Annu. Rev. Microbiol., 2008, 62, 35–51. 112 A. Battesti and E. Bouveret, Mol. Microbiol., 2006, 62, 1048–1063. 113 A. Battesti and E. Bouveret, J. Bacteriol., 2009, 191, 616–624. 114 A. Srivatsan and J. D. Wang, Curr. Opin. Microbiol., 2008, 11, 100– 105. 115 L. U. Magnusson, A. Farewell and T. Nystrom, Trends Microbiol., 2005, 13, 236–242. 116 O. H. Martinez-Costa, M. A. Fernandez-Moreno and F. Malpartida, J. Bacteriol., 1998, 180, 4123–4132. 117 R. Chakraburtty, J. White, E. Takano and M. Bibb, Mol. Microbiol., 1996, 19, 357–368. 118 E. Takano, PhD Thesis, University of East Anglia, Norwich, United Kingdom, 1993. 119 A. Hesketh, J. Sun and M. Bibb, Mol. Microbiol., 2001, 39, 136–144. 120 J. H. Sun, A. Hesketh and M. Bibb, J. Bacteriol., 2001, 183, 3488– 3498. 121 C. Wolz, T. Geiger and C. Goerke, Int. J. Med. Microbiol., 2010, 300, 142–147. 122 L. Krasny and R. L. Gourse, EMBO J., 2004, 23, 4473–4483. 123 K. Ochi, J. Gen. Microbiol., 1986, 132, 299–305. 124 Y. G. Ryu, E. S. Kim, D. W. Kim, S. K. Kim and K. J. Lee, J. Microbiol. Biotechnol., 2007, 17, 305–312. 125 J. P. Gomez-Escribano, J. F. Martin, A. Hesketh, M. J. Bibb and P. Liras, Microbiology, 2008, 154, 744–755. 126 K. Ochi, Biosci., Biotechnol., Biochem., 2007, 71, 1373–1386. 127 T. Hosaka, M. Ohnishi-Kameyama, H. Muramatsu, K. Murakami, Y. Tsurumi, S. Kodani, M. Yoshida, A. Fujie and K. Ochi, Nat. Biotechnol., 2009, 27, 462–464. 128 G. J. Wang, T. Hosaka and K. Ochi, Appl. Environ. Microbiol., 2008, 74, 2834–2840. 129 J. F. Martin and A. L. Demain, Microbiol. Rev., 1980, 44, 230–251. 130 H. Kleinkauf, H. von Dohren, H. Dornauer and G. Nesemann, Regulation of secondary metabolite formation, VCH, Weinheim, 1986. 131 J. F. Martin, J. Bacteriol., 2004, 186, 5197–5201. 132 M. T. Alam, M. E. Merlo, D. A. Hodgson, E. M. H. Wellington, E. Takano and R. Breitling, BMC Genomics, 2010, 11, 9. 133 R. Alduina, L. Lo Piccolo, D. D’Alia, C. Ferraro, N. Gunnarsson, S. Donadio and A. M. Puglia, J. Bacteriol., 2007, 189, 8120–8129. 134 L. M. Reeve and S. Baumberg, Biotechnol. Lett., 1998, 20, 585–589. 135 M. G. Lamarche, B. L. Wanner, S. Crepin and J. Harel, FEMS Microbiol. Rev., 2008, 32, 461–473. 136 O. A. Vershinina and L. V. Znamenskaya, Microbiology, 2002, 71, 497–511. 137 B. L. Wanner, J. Cell. Biochem., 1993, 51, 47–54. 138 A. Rodriguez-Garcia, C. Barreiro, F. Santos-Beneit, A. Sola-Landa and J. F. Martin, Proteomics, 2007, 7, 2410–2429. 139 A. Sola-Landa, R. S. Moura and J. F. Martin, Proc. Natl. Acad. Sci. U. S. A., 2003, 100, 6133–6138. 140 M. Ogura, H. Yamaguchi, K. Yoshida, Y. Fujita and T. Tanaka, Nucleic Acids Res., 2001, 29, 3804–3813. 141 F. Santos-Beneit, A. Rodriguez-Garcia, A. Sola-Landa and J. F. Martin, Mol. Microbiol., 2009, 53–68. 142 S. K. Hong, M. Kito, T. Beppu and S. Horinouchi, J. Bacteriol., 1991, 173, 2311–2318. 143 P. C. Lee, T. Umeyama and S. Horinouchi, Mol. Microbiol., 2002, 43, 1413–1430. 144 A. Tanaka, Y. Takano, Y. Ohnishi and S. Horinouchi, J. Mol. Biol., 2007, 369, 322–333. 145 A. Matsumoto, H. Ishizuka, T. Beppu and S. Horinouchi, Actinomycetologica, 1995, 9, 37–43. 146 B. Floriano and M. Bibb, Mol. Microbiol., 1996, 21, 385–396. 147 M. Vogtli, P. C. Chang and S. N. Cohen, Mol. Microbiol., 1994, 14, 643–653. 148 S. Horinouchi, M. Kito, M. Nishiyama, K. Furuya, S. K. Hong, K. Miyake and T. Beppu, Gene, 1990, 95, 49–56. 149 S. Horinouchi and T. Beppu, Agric. Biol. Chem., 1984, 48, 2131– 2133. 150 W. Lian, K. P. Jayapal, S. Charaniya, S. Mehra, F. Glod, Y. S. Kyung, D. H. Sherman and W. S. Hu, BMC Genomics, 2008, 9, 56. 151 S. Horinouchi, F. Malpartida, D. A. Hopwood and T. Beppu, MGG, Mol. Gen. Genet., 1989, 215, 355–357.
This journal is ª The Royal Society of Chemistry 2011
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
View Online
152 S. Malla, N. P. Niraula, K. Liou and J. K. Sohng, Res. Microbiol., 2010, 161, 109–117. 153 A. Matsumoto, S. K. Hong, H. Ishizuka, S. Horinouchi and T. Beppu, Gene, 1994, 146, 47–56. 154 R. Sawai, A. Suzuki, Y. Takano, P. C. Lee and S. Horinouchi, Gene, 2004, 334, 53–61. 155 T. Umeyama and S. Horinouchi, J. Bacteriol., 2001, 183, 5506– 5512. 156 Y. Lee, K. Kim, J. W. Suh, S. Rhee and Y. Lim, FEMS Microbiol. Lett., 2007, 266, 236–240. 157 J. H. Huh, D. J. Kim, X. Q. Zhao, M. Li, Y. Y. Jo, T. M. Yoon, S. K. Shin, J. H. Yong, Y. W. Ryu, Y. Y. Yang and J. W. Suh, FEMS Microbiol. Lett., 2004, 238, 439–447. 158 D. J. Kim, J. H. Huh, Y. Y. Yang, C. M. Kang, I. H. Lee, C. G. Hyun, S. K. Hong and J. W. Suh, J. Bacteriol., 2003, 185, 592–600. 159 X. Q. Zhao, B. Gust and L. Heide, Arch. Microbiol., 2010, 192, 289– 297. 160 S. K. Shin, D. Xu, H. J. Kwon and J. W. Suh, FEMS Microbiol. Lett., 2006, 259, 53–59. 161 S. Okamoto, A. Lezhava, T. Hosaka, Y. Okamoto-Hosoya and K. Ochi, J. Bacteriol., 2003, 185, 601–609. 162 T. Umeyama, P. C. Lee and S. Horinouchi, Appl. Microbiol. Biotechnol., 2002, 59, 419–425. 163 S. Horinouchi, J. Ind. Microbiol. Biotechnol., 2003, 30, 462–467. 164 J. F. Martin, A. Sola-Landa, F. Santos-Beneit, L. T. FernandezMartinez, C. Prieto and A. Rodiguez-Garcia, Microbial Biotechnol., 2011, 4, 165–174. 165 E. S. Kim, H. J. Hong, C. Y. Choi and S. N. Cohen, J. Bacteriol., 2001, 183, 2969–2969. 166 O. Sekurova, H. Sletta, T. E. Ellingsen, S. Valla and S. Zotchev, FEMS Microbiol. Lett., 1999, 177, 297–304. 167 A. Rodriguez-Garcia, A. Sola-Landa, K. Apel, F. Santos-Beneit and J. F. Martin, Nucleic Acids Res., 2009, 37, 3230–3242. 168 Y. Tiffert, P. Supra, R. Wurm, W. Wohlleben, R. Wagner and J. Reuther, Mol. Microbiol., 2008, 67, 861–880. 169 J. A. Leigh and J. A. Dodsworth, Annu. Rev. Microbiol., 2007, 61, 349–377. 170 C. Harper, D. Hayward, I. Wiid and P. van Heiden, IUBMB Life, 2008, 60, 643–650. 171 J. Reuther and W. Wohlleben, J. Mol. Microbiol. Biotechnol., 2007, 12, 139–146. 172 M. J. Merrick and R. A. Edwards, Microbiol. Rev., 1995, 59, 604– 622. 173 S. Shapiro, in Regulation of secondary metabolism in actinomycetes, ed. S. Shapiro, CRC Press, Boca Raton, FL, 1989. 174 S. Sanchez and A. L. Demain, Enzyme Microb. Technol., 2002, 31, 895–906. 175 E. Krol and A. Becker, Mol. Genet. Genomics, 2004, 272, 1–17. 176 R. A. van Bogelen, E. R. Olson, B. L. Wanner and F. C. Neidhardt, J. Bacteriol., 1996, 178, 4344–4366. 177 K. Nieselt, F. Battke, A. Herbig, P. Bruheim, A. Wentzel, O. M. Jakobsen, H. Sletta, M. T. Alam, M. E. Merlo, J. Moore, W. A. M. Omara, E. R. Morrissey, M. A. Juarez-Hermosillo, A. Rodriguez-Garcia, M. Nentwich, L. Thomas, M. Iqbal, R. Legaie, W. H. Gaze, G. L. Challis, R. C. Jansen, L. Dijkhuizen, D. A. Rand, D. L. Wild, M. Bonin, J. Reuther, W. Wohlleben, M. C. M. Smith, N. J. Burroughs, J. F. Martin, D. A. Hodgson, E. Takano, R. Breitling, T. E. Ellingsen and E. M. H. Wellington, BMC Genomics, 2010, 11, 9. 178 E. M. Panina, A. A. Mironov and M. S. Gelfand, Proc. Natl. Acad. Sci. U. S. A., 2003, 100, 9912–9917. 179 J. H. Shin, S. Y. Oh, S. J. Kim and J. H. Roe, J. Bacteriol., 2007, 189, 4070–4077. 180 A. Hesketh, H. Kock, S. Mootien and M. Bibb, Mol. Microbiol., 2009, 74, 1427–1444. 181 D. Kallifidas, B. Pascoe, G. A. Owen, C. M. Strain-Damerell, H. J. Hong and M. S. B. Paget, J. Bacteriol., 2010, 192, 608–611. 182 K. Hantke, Curr. Opin. Microbiol., 2001, 4, 172–177. 183 S. Tunca, C. Barreiro, J. J. R. Coque and J. F. Martin, FEBS Lett., 2009, 276, 4814–4827. 184 S. Tunca, C. Barreiro, A. Sola-Landa, J. J. R. Coque and J. F. Martin, FEBS Lett., 2007, 274, 1110–1122. 185 S. Sanchez, A. Chavez, A. Forero, Y. Garcia-Huante, A. Romero, M. Sanchez, D. Rocha, B. Sanchez, M. Avalos, S. Guzman-
This journal is ª The Royal Society of Chemistry 2011
186 187 188 189 190 191 192 193 194 195 196 197 198 199
200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218
Trampe, R. Rodriguez-Sanoja, E. Langley and B. Ruiz, J. Antibiot., 2010, 63, 442–459. H. N. Lee, J. H. Im, M. J. Lee, S. Y. Lee and E. S. Kim, Process Biochem., 2009, 44, 373–377. R. K. Bhatnagar, J. L. Doull and L. C. Vining, Can. J. Microbiol., 1988, 34, 1217–1223. J. Cortes, P. Liras, J. M. Castro and J. F. Martin, J. Gen. Microbiol., 1986, 132, 1805–1814. A. Lebrihi, G. Lefebvre and P. Germain, Appl. Microbiol. Biotechnol., 1988, 28, 44–51. L. Escalante, H. Lopez, R. D. Mateos, F. Lara and S. Sanchez, J. Gen. Microbiol., 1982, 128, 2011–2015. O. Bermudez, P. Padilla, C. Huitron and M. E. Flores, FEMS Microbiol. Lett., 1998, 164, 77–82. A. L. Demain and E. Inamine, Bacteriol. Rev., 1970, 34, 1–19. F. Titgemeyer and W. Hillen, Antonie van Leeuwenhoek, 2002, 82, 59–71. J. Deutscher, C. Francke and P. W. Postma, Microbiol. Mol. Biol. Rev., 2006, 70, 939–1031. J. B. Warner and J. S. Lolkema, Microbiol. Mol. Biol. Rev., 2003, 67, 475–490. B. Goerke and J. Stulke, Nat. Rev. Microbiol., 2008, 6, 613–624. H. Nothaft, D. Dresel, A. Willimek, K. Mahr, M. Niederweis and F. Titgemeyer, J. Bacteriol., 2003, 185, 7019–7023. G. P. van Wezel, P. Krabben, B. A. Traag, B. J. F. Keijser, R. Kerste, E. Vijgenboom, J. J. Heijnen and B. Kraal, Appl. Environ. Microbiol., 2006, 72, 5283–5288. S. D. Bentley, K. F. Chater, A. M. Cerdeno-Tarraga, G. L. Challis, N. R. Thomson, K. D. James, D. E. Harris, M. A. Quail, H. Kieser, D. Harper, A. Bateman, S. Brown, G. Chandra, C. W. Chen, M. Collins, A. Cronin, A. Fraser, A. Goble, J. Hidalgo, T. Hornsby, S. Howarth, C. H. Huang, T. Kieser, L. Larke, L. Murphy, K. Oliver, S. O’Neil, E. Rabbinowitsch, M. A. Rajandream, K. Rutherford, S. Rutter, K. Seeger, D. Saunders, S. Sharp, R. Squares, S. Squares, K. Taylor, T. Warren, A. Wietzorrek, J. Woodward, B. G. Barrell, J. Parkhill and D. A. Hopwood, Nature, 2002, 417, 141–147. S. Rigali, M. Schlicht, P. Hoskisson, H. Nothaft, M. Merzbacher, B. Joris and F. Titgemeyer, Nucleic Acids Res., 2004, 32, 3418– 3426. H. Nothaft, S. Rigali, B. Boomsma, M. Swiatek, K. J. McDowall, G. P. van Wezel and F. Titgemeyer, Mol. Microbiol., 2010, 75, 1133–1144. F. Titgemeyer, J. Reizer, A. Reizer and M. H. Saier, Microbiology, 1994, 140, 2349–2354. H. Nothaft, PhD Thesis, University of Erlangen, 2004. S. S. Park, Y. H. Yang, E. Song, E. J. Kim, W. S. Kim, J. K. Sohng, H. C. Lee, K. K. Liou and B. G. Kim, J. Ind. Microbiol. Biotechnol., 2009, 36, 1073–1083. S. Barends, M. Zehl, S. Bialek, E. de Waal, B. A. Traag, J. Willemse, O. N. Jensen, E. Vijgenboom and G. P. van Wezel, EMBO Rep., 2010, 11, 119–125. K. C. Keiler, Annu. Rev. Microbiol., 2008, 62, 133–151. C. S. Hayes and K. C. Keiler, FEBS Lett., 584, pp. 413–419. S. D. Moore and R. T. Sauer, Annu. Rev. Biochem., 2007, 76, 101– 124. S. Barends, B. Kraal and G. P. van Wezel, Wiley Interdisciplinary Reviews: RNA, 2011, 2, 233–246. C. Z. Yang and J. R. Glover, PLoS One, 2009, 4, e4459. P. Paleckova, J. Felsberg, J. Bobek and K. Mikulik, Folia Microbiol., 2007, 52, 463–470. A. Martinez, S. J. Kolvek, J. Hopke, C. L. T. Yip and M. S. Osburne, Appl. Environ. Microbiol., 2005, 71, 1638–1641. G. P. van Wezel, K. Mahr, M. Konig, B. A. Traag, E. F. PimentelSchmitt, A. Willimek and F. Titgemeyer, Mol. Microbiol., 2005, 55, 624–636. D. A. Hodgson, J. Gen. Microbiol., 1982, 128, 2417–2430. E. T. Seno and K. F. Chater, J. Gen. Microbiol., 1983, 129, 1403– 1413. S. Angell, C. G. Lewis, M. J. Buttner and M. J. Bibb, MGG, Mol. Gen. Genet., 1994, 244, 135–143. S. Angell, E. Schwarz and M. J. Bibb, Mol. Microbiol., 1992, 6, 2833–2844. J. H. J. M. Kwakman and P. W. Postma, J. Bacteriol., 1994, 176, 2694–2698.
Nat. Prod. Rep., 2011, 28, 1311–1333 | 1331
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
View Online
219 G. P. van Wezel, M. Konig, K. Mahr, H. Nothaft, A. W. Thomae, M. Bibb and F. Titgemeyer, J. Mol. Microbiol. Biotechnol., 2007, 12, 67–74. 220 H. Chouayekh, H. Nothaft, S. Delaunay, M. Linder, B. Payrastre, N. Seghezzi, F. Titgemeyer and M. J. Virolle, J. Bacteriol., 2007, 189, 741–749. 221 J. Gagnat, H. Chouayekh, C. Gerbaud, F. Francou and M. J. Virolle, Microbiology, 1999, 145, 2303–2312. 222 I. Ramos, S. Guzman, L. Escalante, I. Imriskova, R. RodriguezSanoja, S. Sanchez and E. Langley, Res. Microbiol., 2004, 155, 267–274. 223 S. Guzman, A. Carmona, L. Escalante, I. Imriskova, R. Lopez, R. Rodiguez-Sanoja, B. Ruiz, L. Servin-Gonzalez, S. Sanchez and E. Langley, Microbiology, 2005, 151, 1717–1723. 224 I. Imriskova, R. Arreguin-Espinosa, S. Guzman, R. RodriguezSanoja, E. Langley and S. Sanchez, Res. Microbiol., 2005, 156, 361–366. 225 Z. Hindle and C. P. Smith, Mol. Microbiol., 1994, 12, 737–745. 226 G. P. van Wezel, J. White, P. Young, P. W. Postma and M. J. Bibb, Mol. Microbiol., 1997, 23, 537–549. 227 M. K. Pope, B. Green and J. Westpheling, J. Bacteriol., 1998, 180, 1556–1562. 228 M. K. Pope, B. D. Green and J. Westpheling, Mol. Microbiol., 1996, 19, 747–756. 229 M. Eccleston, R. A. Ali, R. Seyler, J. Westpheling and J. Nodwell, J. Bacteriol., 2002, 184, 4270–4276. 230 M. Eccleston, A. Willems, A. Beveridge and J. R. Nodwell, J. Bacteriol., 2006, 188, 8189–8195. 231 B. A. Traag, G. H. Kelemen and G. P. van Wezel, Mol. Microbiol., 2004, 53, 985–1000. 232 J. Willemse, J. W. Borst, E. De Waal, T. Bisseling and G. P. van Wezel, Genes Dev., 2011, 25, 89–99. 233 G. P. van Wezel, J. van der Meulen, S. Kawamoto, R. G. M. Luiten, H. K. Koerten and B. Kraal, J. Bacteriol., 2000, 182, 5653– 5662. 234 G. P. van Wezel, N. L. McKenzie and J. R. Nodwell, in Complex Enzymes in Microbial Natural Product Biosynthesis, Part A: Overview Articles and Peptides, 2009, pp. 117–141. 235 M. J. Bibb, Curr. Opin. Microbiol., 2005, 8, 208–215. 236 K. F. Chater and S. Horinouchi, Mol. Microbiol., 2003, 48, 9–15. 237 D. A. Hopwood, Annu. Rev. Genet., 2006, 40, 1–23. 238 S. Walter and H. Schrempf, Arch. Microbiol., 2008, 190, 119–127. 239 S. G. Kang, R. G. W. Kenyon, A. C. Ward and K. J. Lee, J. Biotechnol., 1998, 62, 1–10. 240 K. J. Lee, J. Microbiol. Biotechnol., 1998, 8, 1–7. 241 J. R. Nodwell, K. McGovern and R. Losick, Mol. Microbiol., 1996, 22, 881–893. 242 J. R. Nodwell and R. Losick, J. Bacteriol., 1998, 180, 1334–1337. 243 M. I. Hutchings, P. A. Hoskisson, G. Chandra and M. J. Buttner, Microbiology, 2004, 150, 2795–2806. 244 J. F. Martin and P. Liras, Curr. Opin. Microbiol., 2010, 13, 263–273. 245 H. Nishida, Y. Ohnishi, T. Beppu and S. Horinouchi, Environ. Microbiol., 2007, 9, 1986–1994. 246 N. H. Hsiao, M. Gottelt and E. Takano, in Complex Enzymes in Microbial Natural Product Biosynthesis, Part A: Overview Articles and Peptides, 2009, pp. 143–157. 247 K. Ueda, S. Kawai, H. Ogawa, A. Kiyama, T. Kubota, H. Kawanobe and T. Beppu, J. Antibiot., 2000, 53, 979–982. 248 N. H. Hsiao, J. Soding, D. Linke, C. Lange, C. Hertweck, W. Wohlleben and E. Takano, Microbiology, 2007, 153, 1394–1404. 249 E. Takano, R. Chakraburtty, T. Nihira, Y. Yamada and M. J. Bibb, Mol. Microbiol., 2001, 41, 1015–1028. 250 E. Takano, H. Kinoshita, V. Mersinias, G. Bucca, G. Hotchkiss, T. Nihira, C. P. Smith, M. Bibb, W. Wohlleben and K. Chater, Mol. Microbiol., 2005, 56, 465–479. 251 M. Gottelt, S. Kol, J. P. Gomez-Escribano, M. Bibb and E. Takano, Microbiology, 2010, 156, 2343–2353. 252 L. N. Anisova, I. N. Blinova, O. V. Efremenkova, Y. P. Kozmin, V. V. Onoprienko, G. M. Smirnova and A. S. Khokhlov, Izv. Akad. Nauk. SSSR [Biol], 1984, 98–108. 253 N. H. Hsiao, S. Nakayama, M. E. Merlo, M. de Vries, R. Bunet, S. Kitani, T. Nihira and E. Takano, Chem. Biol., 2009, 16, 951–960. 254 E. Takano, Curr. Opin. Microbiol., 2006, 9, 287–294. 255 K. Pawlik, M. Kotowska, K. F. Chater, K. Kuczek and E. Takano, Arch. Microbiol., 2007, 187, 87–99.
1332 | Nat. Prod. Rep., 2011, 28, 1311–1333
256 Y. H. Yang, E. Song, E. J. Kim, K. Lee, W. S. Kim, S. S. Park, J. S. Hahn and B. G. Kim, Appl. Microbiol. Biotechnol., 2009, 82, 501–511. 257 C. Corre, L. J. Song, S. O’Rourke, K. F. Chater and G. L. Challis, Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 17510–17515. 258 E. Recio, A. Colinas, A. Rumbero, J. F. Aparicio and J. F. Martin, J. Biol. Chem., 2004, 279, 41586–41593. 259 C. M. Vicente, J. Santos-Aberturas, S. M. Guerra, T. D. Payero, J. F. Martin and J. F. Aparicio, Microb. Cell Fact., 2009, 8, e33. 260 F. Szeszak, S. Vitalis, F. Toth, G. Valu, J. Fachet and G. Szabo, Arch. Microbiol., 1990, 154, 82–84. 261 Z. Birko, A. Sumegi, A. Vinnai, G. van Wezel, F. Szeszak, S. Vitalis, P. T. Szabo, Z. Kele, T. Janaky and S. Biro, Microbiology, 1999, 145, 2245–2253. 262 S. Biro, Z. Birko and G. P. van Wezel, Antonie van Leeuwenhoek, 2000, 78, 277–285. 263 Z. Birko, S. Bialek, K. Buzas, E. Szajli, B. A. Traag, K. F. Medzihradszky, S. Rigali, E. Vijgenboom, A. Penyige, Z. Kele, G. P. van Wezel and S. Biro, Mol. Cell. Proteomics, 2007, 6, 1248–1256. 264 Z. Birko, M. Swiatek, E. Szajli, K. F. Medzihradszky, E. Vijgenboom, A. Penyige, J. Keseru, G. P. van Wezel and S. Biro, Mol. Cell. Proteomics, 2009, 8, 2396–2403. 265 M. A. Elliot, T. R. Locke, C. M. Galibois and B. K. Leskiw, FEMS Microbiol. Lett., 2003, 225, 35–40. 266 N. K. Gaur, J. Oppenheim and I. Smith, J. Bacteriol., 1991, 173, 678–686. 267 D. B. Kearns, F. Chu, S. S. Branda, R. Kolter and R. Losick, Mol. Microbiol., 2005, 55, 739–749. 268 C. D. den Hengst, N. T. Tran, M. J. Bibb, G. Chandra, B. K. Leskiw and M. J. Buttner, Mol. Microbiol., 2010, 78, 361–379. 269 E. J. Lawlor, H. A. Baylis and K. F. Chater, Genes Dev., 1987, 1, 1305–1310. 270 K. F. Chater and G. Chandra, J. Microbiol., 2008, 46, 1–11. 271 E. Nordhoff, A. M. Krogsdam, H. F. Jorgensen, B. H. Kallipolitis, B. F. C. Clark, P. Roepstorff and K. Kristiansen, Nat. Biotechnol., 1999, 17, 884–888. 272 M. Yaneva and P. Tempst, Anal. Chem., 2003, 75, 6437–6448. 273 A. J. Woo, J. S. Dods, E. Susanto, D. Ulgiati and L. J. Abraham, Mol. Cell. Proteomics, 2002, 1, 472–478. 274 J. A. Stead and K. J. McDowall, Nat. Protoc., 2007, 2, 1839– 1848. 275 J. A. Stead, J. N. Keen and K. J. McDowall, Mol. Cell. Proteomics, 2006, 5, 1697–1702. 276 M. Butala, S. J. W. Busby and D. J. Lee, Nucleic Acids Res., 2009, 37, e37. 277 A. Hesketh, W. Q. Chen, J. Ryding, S. Chang and M. Bibb, GenomeBiology, 2007, 8, e161. 278 J. Q. Huang, C. J. Lih, K. H. Pan and S. N. Cohen, Genes Dev., 2001, 15, 3183–3192. 279 H. Hara, Y. Ohnishi and S. Horinouchi, Microbiology, 2009, 155, 2197–2210. 280 L. Chen, J. Chen, Y. Q. Jiang, W. W. Zhang, W. H. Jiang and Y. H. Lu, FEMS Microbiol. Lett., 2009, 298, 199–207. 281 Y. Ohnishi, J. Ishikawa, H. Hara, H. Suzuki, M. Ikenoya, H. Ikeda, A. Yamashita, M. Hattori and S. Horinouchi, J. Bacteriol., 2008, 190, 4050–4060. 282 A. Hesketh, G. Bucca, E. Laing, F. Flett, G. Hotchkiss, C. P. Smith and K. F. Chater, BMC Genomics, 2007, 8. 283 G. Bucca, E. Laing, V. Mersinias, N. Allenby, D. Hurd, J. Holdstock, V. Brenner, M. Harrison and C. P. Smith, GenomeBiology, 2009, 10, e5. 284 D. C. Grainger, D. J. Lee and S. J. W. Busby, Curr. Opin. Microbiol., 2009, 12, 531–535. 285 A. Manteca, H. R. Jung, V. Schwammle, O. N. Jensen and J. Sanchez, J. Proteome Res., 2010, 9, 4801–4811. 286 A. Manteca, J. Sanchez, H. R. Jung, V. Schwammle and O. N. Jensen, Mol. Cell. Proteomics, 2010, 9, 1423–1436. 287 S. B. Bumpus, B. S. Evans, P. M. Thomas, I. Ntai and N. L. Kelleher, Nat. Biotechnol., 2009, 27, 951–956. 288 M. V. Joshi, S. G. Mann, H. Antelmann, D. A. Widdick, J. K. Fyans, G. Chandra, M. I. Hutchings, I. Toth, M. Hecker, R. Loria and T. Palmer, Mol. Microbiol., 2010, 77, 252–271. 289 C. X. Wang, X. H. Long, X. M. Mao, H. J. Dong, L. X. Xu and Y. Q. Li, Microbiol. Res., 2010, 165, 221–231.
This journal is ª The Royal Society of Chemistry 2011
Downloaded by Rijksuniversiteit Leiden on 23 June 2011 Published on 25 May 2011 on http://pubs.rsc.org | doi:10.1039/C1NP00003A
View Online
290 D. W. Kim, K. Chater, K. J. Lee and A. Hesketh, J. Bacteriol., 2005, 187, 2957–2966. 291 R. Aebersold and M. Mann, Nature, 2003, 422, 198–207. 292 A. Gorg, W. Weiss and M. J. Dunn, Proteomics, 2004, 4, 3665–3685. 293 S. E. Ong and M. Mann, Nat. Chem. Biol., 2005, 1, 252–262. 294 B. Domon and R. Aebersold, Science, 2006, 312, 212–217. 295 R. Baran, W. Reindl and T. R. Northen, Curr. Opin. Microbiol., 2009, 12, 547–552. 296 H. B. Kim, C. P. Smith, J. Micklefield and F. Mavituna, Metab. Eng., 2004, 6, 313–325. 297 J. M. Otero and J. Nielsen, Biotechnol. Bioeng., 2010, 105, 439–460. 298 J. S. Rokem, A. E. Lantz and J. Nielsen, Nat. Prod. Rep., 2007, 24, 1262–1287. 299 R. H. Baltz, J. Ind. Microbiol. Biotechnol., 2010, 37, 759–772. 300 G. W. Hanlon, Int. J. Antimicrob. Agents, 2007, 30, 118–128. 301 L. A. Marraffini and E. J. Sontheimer, Nat. Rev. Genet., 2010, 11, 181–190. 302 J. van der Oost, M. M. Jore, E. R. Westra, M. Lundgren and S. J. J. Brouns, Trends Biochem. Sci., 2009, 34, 401–407. 303 Y. X. Zhang, K. Perry, V. A. Vinci, K. Powell, W. P. C. Stemmer and S. B. del Cardayre, Nature, 2002, 415, 644–646. 304 J. S. Feitelson, F. Malpartida and D. A. Hopwood, J. Gen. Microbiol., 1985, 131, 2431–2441. 305 K. E. Narva and J. S. Feitelson, J. Bacteriol., 1990, 172, 326–333. 306 L. Chen, Y. H. Lu, J. Chen, W. W. Zhang, D. Shu, Z. J. Qin, S. Yang and W. H. Jiang, Appl. Microbiol. Biotechnol., 2008, 80, 277–286. 307 N. J. Ryding, T. B. Anderson and W. C. Champness, J. Bacteriol., 2002, 184, 794–805. 308 Y. H. Yang, J. N. Kim, E. J. Song, E. Kim, M. K. Oh and B. G. Kim, Appl. Microbiol. Biotechnol., 2008, 80, 709–717. 309 R. Chakraburtty and M. Bibb, J. Bacteriol., 1997, 179, 5854–5861. 310 K. Ochi, J. Gen. Microbiol., 1990, 136, 2405–2412. 311 K. Ochi, J. Bacteriol., 1990, 172, 4008–4016. 312 K. S. Kelly, K. Ochi and G. H. Jones, J. Bacteriol., 1991, 173, 2297–2300. 313 C. X. Lai, J. Xu, Y. Tozawa, Y. Okamoto-Hosoya, X. S. Yao and K. Ochi, Microbiology, 2002, 148, 3365–3373. 314 H. Onaka, T. Nakagawa and S. Horinouchi, Mol. Microbiol., 1998, 28, 743–753. 315 D. L. Xu, N. Seghezzi, C. Esnault and M. J. Virolle, Appl.Environ. Microbiol., 2010, 76, 7741–7753. 316 T. Umeyama, P. C. Lee, K. Ueda and S. Horinouchi, Microbiology, 1999, 145, 2281–2292. 317 A. Tomono, M. Mashiko, T. Shimazu, H. Inoue, H. Nagasawa, M. Yoshida, Y. Ohnishi and S. Horinouchi, J. Antibiot., 2006, 59, 117–123.
This journal is ª The Royal Society of Chemistry 2011
318 A. Sola-Landa, A. Rodriguez-Garcia, E. Franco-Dominguez and J. F. Martin, Mol. Microbiol., 2005, 56, 1373–1385. 319 M. V. Mendes, S. Tunca, N. Anton, E. Recio, A. Sola-Landa, J. F. Aparicio and J. F. Martin, Metab. Eng., 2007, 9, 217– 227. 320 A. Sola-Landa, A. Rodriguez-Garci, A. K. Apel and J. F. Martin, Nucleic Acids Res., 2008, 36, 1358–1368. 321 G. H. Kelemen and M. J. Buttner, Curr. Opin. Microbiol., 1998, 1, 656–662. 322 K. F. Chater, Curr. Opin. Microbiol., 2001, 4, 667–673. 323 D. Shu, L. Chen, W. H. Wang, Z. Y. Yu, C. Ren, W. W. Zhang, S. Yang, Y. H. Lu and W. H. Jiang, Appl. Microbiol. Biotechnol., 2009, 81, 1149–1160. 324 H. Ishizuka, S. Horinouchi, H. M. Kieser, D. A. Hopwood and T. Beppu, J. Bacteriol., 1992, 174, 7585–7594. 325 B. Price, T. Adamidis, R. Q. Kong and W. Champness, J. Bacteriol., 1999, 181, 6142–6151. 326 W. J. Xu, J. Q. Huang, R. Lin, J. Shi and S. N. Cohen, Mol. Microbiol., 2010, 75, 781–791. 327 W. J. Xu, J. Q. Huang and S. N. Cohen, J. Bacteriol., 2008, 190, 5526–5530. 328 U. Park, J. W. Suh and S. K. Hong, J. Microbiol. Biotechnol., 2000, 10, 169–175. 329 H. M. Chang, M. Y. Chen, Y. T. Shieh, M. J. Bibb and C. W. Chen, Mol. Microbiol., 1996, 21, 1075–1085. 330 C. X. Wang, H. X. Ge, H. J. Dong, C. G. Zhu, Y. Q. Li, J. Zheng and P. L. Cen, Biologia, 2007, 62, 511–516. 331 W. C. Li, X. Ying, Y. Z. Guo, Z. Yu, X. F. Zhou, Z. X. Deng, H. Kieser, K. F. Chater and M. F. Tao, J. Bacteriol., 2006, 188, 8368–8375. 332 X. J. Wang, S. L. Guo, W. Q. Guo, D. Xi and W. S. Xiang, J. Antibiot., 2009, 62, 309–313. 333 L. Zhang, W. C. Li, C. H. Zhao, K. F. Chater and M. F. Tao, Weishengwu Xuebao, 2007, 47, 849–854. 334 Y. H. Lu, W. H. Wang, D. Shu, W. W. Zhang, L. Chen, Z. J. Qin, S. Yang and W. H. Jiang, Appl. Microbiol. Biotechnol., 2007, 77, 625–635. 335 X. J. Ou, B. Zhang, L. Zhang, G. P. Zhao and X. M. Ding, Appl. Environ. Microbiol., 2009, 75, 2158–2165. 336 S. H. Kang, J. Q. Huang, H. N. Lee, Y. A. Hur, S. N. Cohen and E. S. Kim, J. Bacteriol., 2007, 189, 4315–4319. 337 B. A. Traag and G. P. van Wezel, Antonie van Leeuwenhoek, 2008, 94, 85–97. 338 G. E. Crooks, G. Hon, J. M. Chandonia and S. E. Brenner, Genome Res., 2004, 14, 1188–1190.
Nat. Prod. Rep., 2011, 28, 1311–1333 | 1333