Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000194.1:
Cluster 1Polyketide121283

BGC0000194, actinorhodin biosynthetic gene cluster from Streptomyces coelicolor. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: Actinorhodin
PubChem ID: 5280985
ChEBI ID: 2448
ChemSpider ID: 16735642
SMILES string: Copy to clipboard
Molecular formula: C32H26O14
Average molecular mass: 634.54044 Da
Molecular activity: Antibacterial

Class-specific details

Biosynthetic class(es):
Polyketide
Polyketide subclass:
Benzoisochromanequinone (cyclic)
Polyketide synthase subclass:
Type II
Starter unit:
Malonyl-CoA
Polyketide synthase / ketosynthase-encoding genes:
SCO5087
Genes involved in folding/cyclization:
SCO5090,SCO5091

Gene cluster description

actinorhodin (BGC0000194). Gene Cluster 1. Biosynthetic class = Polyketide. GenBank AL645882, positions 5513809-5535091. Click on genes for more information.

Legend:

biosynthetic genes
transport-related genes
regulatory genes
other genes

Homologous known gene clusters

General MIBiG information on this cluster

Complete gene cluster sequence?complete
Evidence for cluster-compound connection:Knock-out studies, Enzymatic assays, Heterologous expression, Gene expression correlated with compound production, Sequence-based prediction
MIxS-compliance:Unknown
Contact for this cluster:Marnix Medema (Wageningen University)

Literature references

1. Taguchi T et al. (2015) Structure and biosynthetic implication of 5R-(N-acetyl-L-cysteinyl)-14S-hydroxy-dihydrokalafungin from a mutant of the actVA-ORF4 gene for actinorhodin biosynthesis in Streptomyces coelicolor A3(2). J Antibiot (Tokyo) 68(7):481-3. doi: 10.1038/ja.2015.13. Epub 2015 Feb
2. Javidpour P et al. (2013) The determinants of activity and specificity in actinorhodin type II polyketide ketoreductase. Chem Biol 20(10):1225-34. doi: 10.1016/j.chembiol.2013.07.016. Epub
3. Taguchi T et al. (2013) Biosynthetic conclusions from the functional dissection of oxygenases for biosynthesis of actinorhodin and related Streptomyces antibiotics. Chem Biol 20(4):510-20. doi: 10.1016/j.chembiol.2013.03.007.
4. Xu Y et al. (2012 TI) A two-step mechanism for the activation of actinorhodin export and resistance in Streptomyces coelicolor. MBio 3(5):e00191-12. doi: 10.1128/mBio.00191-12.
5. Taguchi T et al. (2012) Identification of the actinorhodin monomer and its related compound from a deletion mutant of the actVA-ORF4 gene of Streptomyces coelicolor A3(2). Bioorg Med Chem Lett 22(15):5041-5. doi: 10.1016/j.bmcl.2012.06.005.
6. Taguchi T et al. (2011) Epoxyquinone formation catalyzed by a two-component flavin-dependent monooxygenase involved in biosynthesis of the antibiotic actinorhodin. Chembiochem 12(18):2767-73. doi: 10.1002/cbic.201100571. Epub 2011
7. Javidpour P et al. (2011) Structural and biochemical analyses of regio- and stereospecificities observed in a type II polyketide ketoreductase. Biochemistry 50(21):4638-49. doi: 10.1021/bi200335f. Epub 2011 May
8. Beltran-Alvarez P et al. (2009) Preliminary kinetic analysis of acyl carrier protein-ketoacylsynthase interactions in the actinorhodin minimal polyketide synthase. Mol Biosyst 5(5):511-8. doi: 10.1039/b821844g. Epub 2009 Mar 20.
9. Evans SE et al. (2009) Probing the Interactions of early polyketide intermediates with the Actinorhodin ACP from S. coelicolor A3(2). J Mol Biol 389(3):511-28. doi: 10.1016/j.jmb.2009.03.072. Epub 2009
10. Das A, Khosla C. (2009) Biosynthesis of aromatic polyketides in bacteria. Acc Chem Res 42(5):631-9. doi: 10.1021/ar8002249.
11. Okamoto S et al. (2009) Biosynthesis of actinorhodin and related antibiotics: discovery of alternative routes for quinone formation encoded in the act gene cluster. Chem Biol 16(2):226-36. doi: 10.1016/j.chembiol.2009.01.015.
12. Tahlan K et al. (2008) Ligand recognition by ActR, a TetR-like regulator of actinorhodin export. J Mol Biol 383(4):753-61. doi: 10.1016/j.jmb.2008.08.081. Epub 2008
13. Xu XP et al. (2008) Localization of the ActIII actinorhodin polyketide ketoreductase to the cell wall. FEMS Microbiol Lett 287(1):15-21. doi:
14. Valton J et al. (2008) Mechanism and regulation of the Two-component FMN-dependent monooxygenase ActVA-ActVB from Streptomyces coelicolor. J Biol Chem 283(16):10287-96. doi: 10.1074/jbc.M709730200. Epub 2008
15. Willems AR et al. (2008) Crystal structures of the Streptomyces coelicolor TetR-like protein ActR alone and in complex with actinorhodin or the actinorhodin biosynthetic precursor (S)-DNPA. J Mol Biol 376(5):1377-87. doi: 10.1016/j.jmb.2007.12.061. Epub 2008
16. Korman TP et al. (2008) Inhibition kinetics and emodin cocrystal structure of a type II polyketide ketoreductase. Biochemistry 47(7):1837-47. doi: 10.1021/bi7016427. Epub 2008 Jan
17. Beltran-Alvarez P et al. (2007) Dissecting the component reactions catalyzed by the actinorhodin minimal polyketide synthase. Biochemistry 46(50):14672-81. Epub 2007 Nov 23.
18. Ahn SK et al. (2007) Investigation of transcription repression and small-molecule responsiveness by TetR-like transcription factors using a heterologous Escherichia coli-based assay. J Bacteriol 189(18):6655-64. Epub 2007 Jul 20.
19. Itoh T et al. (2007) Actinorhodin biosynthesis: structural requirements for post-PKS tailoring intermediates revealed by functional analysis of ActVI-ORF1 reductase. Biochemistry 46(27):8181-8. Epub 2007 Jun 19.
20. Tahlan K et al. (2007) Initiation of actinorhodin export in Streptomyces coelicolor. Mol Microbiol 63(4):951-61.
21. Taguchi T et al. (2007) Possible involvement of ActVI-ORFA in transcriptional regulation of actVI tailoring-step genes for actinorhodin biosynthesis. FEMS Microbiol Lett 269(2):234-9. Epub 2007 Jan 15.
22. Arthur CJ et al. (2005) Self-malonylation is an intrinsic property of a chemically synthesized type II polyketide synthase acyl carrier protein. Biochemistry 44(46):15414-21.
23. Uguru GC et al. (2005) Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol Microbiol 58(1):131-50.
24. Taguchi T et al. (2004) Remarkably different structures and reaction mechanisms of ketoreductases for the opposite stereochemical control in the biosynthesis of BIQ antibiotics. Bioorg Med Chem 12(22):5917-27.
25. Hadfield AT et al. (2004) The crystal structure of the actIII actinorhodin polyketide reductase: proposed mechanism for ACP and polyketide binding. Structure 12(10):1865-75.
26. Keatinge-Clay AT et al. (2004) An antibiotic factory caught in action. Nat Struct Mol Biol 11(9):888-93. Epub 2004 Aug 1.
27. Hesketh AR et al. (2002) Primary and secondary metabolism, and post-translational protein modifications, as portrayed by proteomic analysis of Streptomyces coelicolor. Mol Microbiol 46(4):917-32.
28. Hopwood DA. (1997) Genetic Contributions to Understanding Polyketide Synthases. Chem Rev 97(7):2465-2498.
29. Taguchi T et al. (2000) Chemical characterisation of disruptants of the Streptomyces coelicolor A3(2) actVI genes involved in actinorhodin biosynthesis. J Antibiot (Tokyo) 53(2):144-52.
30. Dreier J, Khosla C. (2000) Mechanistic analysis of a type II polyketide synthase. Role of conserved residues in the beta-ketoacyl synthase-chain length factor heterodimer. Biochemistry 39(8):2088-95.
31. Bisang C et al. (1999) A chain initiation factor common to both modular and aromatic polyketide synthases. Nature 401(6752):502-5.
32. Ichinose K et al. (1999) Proof that the ACTVI genetic region of Streptomyces coelicolor A3(2) is involved in stereospecific pyran ring formation in the biosynthesis of actinorhodin. Bioorg Med Chem Lett 9(3):395-400.
33. Kendrew SG et al. (1997) Identification of a monooxygenase from Streptomyces coelicolor A3(2) involved in biosynthesis of actinorhodin: purification and characterization of the recombinant enzyme. J Bacteriol 179(13):4305-10.
34. Bystrykh LV et al. (1996) Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2). J Bacteriol 178(8):2238-44.
35. Kendrew SG et al. (1995) Identification of a flavin:NADH oxidoreductase involved in the biosynthesis of actinorhodin. Purification and characterization of the recombinant enzyme. J Biol Chem 270(29):17339-43.
36. Fernandez-Moreno MA et al. (1994) DNA sequence and functions of the actVI region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor A3(2). J Biol Chem 269(40):24854-63.
37. Gramajo HC et al. (1993) Stationary-phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated. Mol Microbiol 7(6):837-45.
38. Fernandez-Moreno MA et al. (1992) Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin. J Biol Chem 267(27):19278-90.
39. Caballero JL et al. (1991) Organisation and functions of the actVA region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor. Mol Gen Genet 230(3):401-12.
40. Caballero JL et al. (1991) Transcriptional organization and regulation of an antibiotic export complex in the producing Streptomyces culture. Mol Gen Genet 228(3):372-80.
41. Fernandez-Moreno MA et al. (1991) The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. Cell 66(4):769-80.
42. Bartel PL et al. (1990) Biosynthesis of anthraquinones by interspecies cloning of actinorhodin biosynthesis genes in streptomycetes: clarification of actinorhodin gene functions. J Bacteriol 172(9):4816-26.
43. Hallam SE et al. (1988) Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor. Gene 74(2):305-20.