BGC0000194

BGC0000194: actinorhodin biosynthetic gene cluster from Streptomyces coelicolor A3(2)

View antiSMASH-generated output

Download Cluster GenBank file

Download region SVG

Location: 5,513,809 - 5,535,091 nt. (total: 21,283 nt).
This entry is originally from NCBI GenBank AL645882.2.

Legend:

core biosynthetic genes

additional biosynthetic genes

transport-related genes

regulatory genes

other genes

resistance

TTA codons

reset view

zoom to selection

Gene details

Select a gene to view the details available for it

General

Compounds

Genes

Biosynthesis

History

NRPS/PKS domains

KnownClusterBlast

General information about the BGC

MIBiG accession	BGC0000194
Short description	actinorhodin biosynthetic gene cluster from Streptomyces coelicolor A3(2)
Status	Quality: questionable The quality level of this entry. Status: active The status of this entry. Completeness: complete Whether the entry covers everything needed for the pathway producing the compound(s)
Biosynthetic class(es)	PKS (Type II aromatic)
Loci	AL645882.2 5513809 - 5535091 via Knock-out studies, Enzymatic assays, Heterologous expression, Gene expression correlated with compound production
Compounds	actinorhodin
Species	Streptomyces coelicolor A3(2) [taxonomy]
References	[1] Total Synthesis of Actinorhodin. Ninomiya, M et al., Angewandte Chemie (2019) DOI:10.1002/ange.201814172 [2] Actinomycetenfarbstoffe, IV. Mitteil.: über die Konstitution des Actinorhodins und die Isolierung des Proto‐actinorhodins. Brockmann, H et al., Chemische Berichte (1955) DOI:10.1002/cber.19550880607 [3] Proof that the ACTVI genetic region of Streptomyces coelicolor A3(2) is involved in stereospecific pyran ring formation in the biosynthesis of actinorhodin. Ichinose K et al., Bioorg Med Chem Lett (1999) PMID:10091691 [4] A chain initiation factor common to both modular and aromatic polyketide synthases. Bisang C et al., Nature (1999) PMID:10519556 [5] Mechanistic analysis of a type II polyketide synthase. Role of conserved residues in the beta-ketoacyl synthase-chain length factor heterodimer. Dreier J et al., Biochemistry (2000) PMID:10684659 [6] Chemical characterisation of disruptants of the Streptomyces coelicolor A3(2) actVI genes involved in actinorhodin biosynthesis. Taguchi T et al., J Antibiot (Tokyo) (2000) PMID:10805574 [7] Genetic Contributions to Understanding Polyketide Synthases. Hopwood DA, Chem Rev (1997) PMID:11851466 [8] Primary and secondary metabolism, and post-translational protein modifications, as portrayed by proteomic analysis of Streptomyces coelicolor. Hesketh AR et al., Mol Microbiol (2002) PMID:12421300 [9] Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin. Fernández-Moreno MA et al., J Biol Chem (1992) PMID:1527048 [10] An antibiotic factory caught in action. Keatinge-Clay AT et al., Nat Struct Mol Biol (2004) PMID:15286722 [11] The crystal structure of the actIII actinorhodin polyketide reductase: proposed mechanism for ACP and polyketide binding. Hadfield AT et al., Structure (2004) PMID:15458634 [12] Remarkably different structures and reaction mechanisms of ketoreductases for the opposite stereochemical control in the biosynthesis of BIQ antibiotics. Taguchi T et al., Bioorg Med Chem (2004) PMID:15498668 [13] Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Uguru GC et al., Mol Microbiol (2005) PMID:16164554 [14] Self-malonylation is an intrinsic property of a chemically synthesized type II polyketide synthase acyl carrier protein. Arthur CJ et al., Biochemistry (2005) PMID:16285746 [15] Transcriptional organization and regulation of an antibiotic export complex in the producing Streptomyces culture. Caballero JL et al., Mol Gen Genet (1991) PMID:1716725 [16] Possible involvement of ActVI-ORFA in transcriptional regulation of actVI tailoring-step genes for actinorhodin biosynthesis. Taguchi T et al., FEMS Microbiol Lett (2007) PMID:17227452 [17] Initiation of actinorhodin export in Streptomyces coelicolor. Tahlan K et al., Mol Microbiol (2007) PMID:17338074 [18] Actinorhodin biosynthesis: structural requirements for post-PKS tailoring intermediates revealed by functional analysis of ActVI-ORF1 reductase. Itoh T et al., Biochemistry (2007) PMID:17579485 [19] Investigation of transcription repression and small-molecule responsiveness by TetR-like transcription factors using a heterologous Escherichia coli-based assay. Ahn SK et al., J Bacteriol (2007) PMID:17644591 [20] Organisation and functions of the actVA region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor. Caballero JL et al., Mol Gen Genet (1991) PMID:1766437 [21] Dissecting the component reactions catalyzed by the actinorhodin minimal polyketide synthase. Beltran-Alvarez P et al., Biochemistry (2007) PMID:18034463 [22] Inhibition kinetics and emodin cocrystal structure of a type II polyketide ketoreductase. Korman TP et al., Biochemistry (2008) PMID:18205400 [23] Crystal structures of the Streptomyces coelicolor TetR-like protein ActR alone and in complex with actinorhodin or the actinorhodin biosynthetic precursor (S)-DNPA. Willems AR et al., J Mol Biol (2008) PMID:18207163 [24] Mechanism and regulation of the Two-component FMN-dependent monooxygenase ActVA-ActVB from Streptomyces coelicolor. Valton J et al., J Biol Chem (2008) PMID:18245777 [25] Localization of the ActIII actinorhodin polyketide ketoreductase to the cell wall. Xu XP et al., FEMS Microbiol Lett (2008) PMID:18691223 [26] The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. Fernández-Moreno MA et al., Cell (1991) PMID:1878971 [27] Ligand recognition by ActR, a TetR-like regulator of actinorhodin export. Tahlan K et al., J Mol Biol (2008) PMID:18804114 [28] Biosynthesis of actinorhodin and related antibiotics: discovery of alternative routes for quinone formation encoded in the act gene cluster. Okamoto S et al., Chem Biol (2009) PMID:19246012 [29] Biosynthesis of aromatic polyketides in bacteria. Das A et al., Acc Chem Res (2009) PMID:19292437 [30] Probing the Interactions of early polyketide intermediates with the Actinorhodin ACP from S. coelicolor A3(2). Evans SE et al., J Mol Biol (2009) PMID:19361520 [31] Preliminary kinetic analysis of acyl carrier protein-ketoacylsynthase interactions in the actinorhodin minimal polyketide synthase. Beltran-Alvarez P et al., Mol Biosyst (2009) PMID:19381365 [32] Structural and biochemical analyses of regio- and stereospecificities observed in a type II polyketide ketoreductase. Javidpour P et al., Biochemistry (2011) PMID:21506596 [33] Epoxyquinone formation catalyzed by a two-component flavin-dependent monooxygenase involved in biosynthesis of the antibiotic actinorhodin. Taguchi T et al., Chembiochem (2011) PMID:22086671 [34] Identification of the actinorhodin monomer and its related compound from a deletion mutant of the actVA-ORF4 gene of Streptomyces coelicolor A3(2). Taguchi T et al., Bioorg Med Chem Lett (2012) PMID:22765902 [35] A two-step mechanism for the activation of actinorhodin export and resistance in Streptomyces coelicolor. Xu Y et al., mBio (2012) PMID:23073761 [36] Biosynthetic conclusions from the functional dissection of oxygenases for biosynthesis of actinorhodin and related Streptomyces antibiotics. Taguchi T et al., Chem Biol (2013) PMID:23601640 [37] Biosynthesis of anthraquinones by interspecies cloning of actinorhodin biosynthesis genes in streptomycetes: clarification of actinorhodin gene functions. Bartel PL et al., J Bacteriol (1990) PMID:2394677 [38] The determinants of activity and specificity in actinorhodin type II polyketide ketoreductase. Javidpour P et al., Chem Biol (2013) PMID:24035284 [39] Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor. Hallam SE et al., Gene (1988) PMID:2469622 [40] 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). Taguchi T et al., J Antibiot (Tokyo) (2015) PMID:25690356 [41] Identification of a flavin:NADH oxidoreductase involved in the biosynthesis of actinorhodin. Purification and characterization of the recombinant enzyme. Kendrew SG et al., J Biol Chem (1995) PMID:7615536 [42] Stationary-phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated. Gramajo HC et al., Mol Microbiol (1993) PMID:7683365 [43] DNA sequence and functions of the actVI region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor A3(2). Fernández-Moreno MA et al., J Biol Chem (1994) PMID:7929165 [44] Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2). Bystrykh LV et al., J Bacteriol (1996) PMID:8636024 [45] Identification of a monooxygenase from Streptomyces coelicolor A3(2) involved in biosynthesis of actinorhodin: purification and characterization of the recombinant enzyme. Kendrew SG et al., J Bacteriol (1997) PMID:9209048

Chemical products information

actinorhodin Evidence: NMR [1], Chemical derivatisation [2]

Copy SMILES

C₃₂H₂₆O₁₄

Chemical database entries
ChEBI
ChemSpider
PubCHEM

List of genes involved in compound(s) production

Identifiers	Position	Product	Extra
CAC37459.1 SCO5071	5513809 - 5514249 (-)	hydroxylacyl-CoA dehydrogenase	copy AA seq copy Nt seq
CAC37460.1 SCO5072	5514323 - 5515246 (+)	hydroxylacyl-CoA dehydrogenase	copy AA seq copy Nt seq
CAC37461.1 SCO5073	5515243 - 5516232 (+)	putative oxidoreductase	copy AA seq copy Nt seq
CAC37462.1 SCO5074	5516299 - 5516943 (+)	putative dehydratase	copy AA seq copy Nt seq
CAD55222.1 SCO5075	5516977 - 5517897 (+)	putative oxidoreductase	copy AA seq copy Nt seq
CAC44189.1 SCO5076	5517894 - 5519495 (+)	integral membrane protein	copy AA seq copy Nt seq
CAC44190.1 SCO5077	5519497 - 5519892 (+)	hypothetical protein	copy AA seq copy Nt seq
CAC44191.1 SCO5078	5519987 - 5520832 (+)	hypothetical protein	copy AA seq copy Nt seq
CAC44192.1 SCO5079	5520857 - 5521741 (+)	conserved hypothetical protein	copy AA seq copy Nt seq
CAC44193.1 SCO5080	5521738 - 5522883 (+)	putative hydrolase	copy AA seq copy Nt seq
CAC44194.1 SCO5081	5522876 - 5523217 (+)	hypothetical protein	copy AA seq copy Nt seq
CAC44195.1 SCO5082	5523183 - 5523962 (-)	putative transcriptional regulatory protein	copy AA seq copy Nt seq
CAC44196.1 SCO5083	5524073 - 5525809 (+)	putative actinorhodin transporter	copy AA seq copy Nt seq
CAC44197.1 SCO5084	5525809 - 5527944 (+)	putative membrane protein	copy AA seq copy Nt seq
CAC44198.1 SCO5085	5528094 - 5528861 (+)	actinorhodin cluster activator protein	copy AA seq copy Nt seq
CAC44199.1 SCO5086	5528935 - 5529720 (-)	ketoacyl reductase	copy AA seq copy Nt seq
CAC44200.1 SCO5087	5529801 - 5531204 (+)	actinorhodin polyketide beta-ketoacyl synthase alpha subunit	copy AA seq copy Nt seq
CAC44201.1 SCO5088	5531201 - 5532424 (+)	actinorhodin polyketide beta-ketoacyl synthase beta subunit	copy AA seq copy Nt seq
CAC44202.1 SCO5089	5532449 - 5532709 (+)	actinorhodin polyketide synthase acyl carrier protein	copy AA seq copy Nt seq
CAC44203.1 SCO5090	5532706 - 5533656 (+)	actinorhodin polyketide synthase bifunctional cyclase/dehydratase	copy AA seq copy Nt seq
CAC44204.1 SCO5091	5533653 - 5534546 (+)	cyclase	copy AA seq copy Nt seq
CAC44205.1 SCO5092	5534558 - 5535091 (+)	actinorhodin polyketide putative dimerase	copy AA seq copy Nt seq

Biosynthesis information

Annotation changelog

Entry version: next

Date

Changes

Submitters

Reviewers

2024-05-14

MIBiG v4 annotathon

(ID: 7ZPV7YL7LI6WACA7MW4GA2DX)
(ID: 6AM7JJ6YDANL6JX7PSA4P3HZ)
(ID: MGLE5JJ3S32DQA3YR5WPYH4W)

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

Entry version: 4

Date

Changes

Submitters

Reviewers

2022-10-07

Update chemical activity to schema version 2.11

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

Entry version: 3

Date

Changes

Submitters

Reviewers

2022-09-15

Split gene names containing multiple alternatives

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

Entry version: 2

Date

Changes

Submitters

Reviewers

2019-10-16

Migrated from v1.4

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

Entry version: 1

Date

Changes

Submitters

Reviewers

2015-06-12

Submitted

(ID: AK53UXEU2X7JUZMX7VY3GZAO)

(ID: AAAAAAAAAAAAAAAAAAAAAAAA)

Detailed domain annotation

Selected features only

Show module domains

Similar known gene clusters from MIBiG 4.0