BGC0000965

BGC0000965: C-1027 biosynthetic gene cluster from Streptomyces globisporus

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Location: 1 - 85,163 nt. (total: 85,163 nt).
This entry is originally from NCBI GenBank AY048670.1.

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core biosynthetic genes

additional biosynthetic genes

transport-related genes

regulatory genes

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Gene details

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General

Compounds

Genes

Polyketide

History

NRPS/PKS domains

KnownClusterBlast

General information about the BGC

MIBiG accession	BGC0000965
Short description	C-1027 biosynthetic gene cluster from Streptomyces globisporus
Status	Minimal annotation: no A minimal annotation only contains information on the BGC loci and one or more linked chemical product(s) Completeness: complete Whether the loci encodes everything needed for the pathway producing the compound(s)
Biosynthetic class(es)	Polyketide (Enediyine)
Loci	NCBI GenBank: AY048670.1
Compounds	C-1027
Species	Streptomyces globisporus [taxonomy]
References	Biosynthesis of the enediyne antitumor antibiotic C-1027. Liu W et al., Science (2002) PMID:12183628 Genes for production of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus are clustered with the cagA gene that encodes the C-1027 apoprotein. Liu W et al., Antimicrob Agents Chemother (2000) PMID:10639366 A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. Christenson SD et al., J Am Chem Soc (2003) PMID:12785829 Kinetic analysis of the 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. Christenson SD et al., Biochemistry (2003) PMID:14580219 Biochemical characterization of the SgcA1 alpha-D-glucopyranosyl-1-phosphate thymidylyltransferase from the enediyne antitumor antibiotic C-1027 biosynthetic pathway and overexpression of sgcA1 in Streptomyces globisporus to improve C-1027 production. Murrell JM et al., J Nat Prod (2004) PMID:14987060 Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring beta-amino acyl-S-carrier protein intermediates. Van Lanen SG et al., J Am Chem Soc (2005) PMID:16104723 Substrate specificity of the adenylation enzyme SgcC1 involved in the biosynthesis of the enediyne antitumor antibiotic C-1027. Van Lanen SG et al., J Biol Chem (2006) PMID:16887797 Single chemical modifications of the C-1027 enediyne core, a radiomimetic antitumor drug, affect both drug potency and the role of ataxia-telangiectasia mutated in cellular responses to DNA double-strand breaks. Kennedy DR et al., Cancer Res (2007) PMID:17234789 The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway. Christianson CV et al., Biochemistry (2007) PMID:17516659 Regiospecific chlorination of (S)-beta-tyrosyl-S-carrier protein catalyzed by SgcC3 in the biosynthesis of the enediyne antitumor antibiotic C-1027. Lin S et al., J Am Chem Soc (2007) PMID:17887753 The mechanism of MIO-based aminomutases in beta-amino acid biosynthesis. Christianson CV et al., J Am Chem Soc (2007) PMID:18052279 Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism. Van Lanen SG et al., Proc Natl Acad Sci U S A (2008) PMID:18182490 Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027. Lin S et al., J Am Chem Soc (2008) PMID:18426211 A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis. Lin S et al., Proc Natl Acad Sci U S A (2009) PMID:19246381 Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027. Van Lanen SG et al., FEMS Microbiol Lett (2009) PMID:19817865 Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis. Lin S et al., J Am Chem Soc (2009) PMID:19856960 Manipulation of pathway regulation in Streptomyces globisporus for overproduction of the enediyne antitumor antibiotic C-1027. Chen Y et al., J Antibiot (Tokyo) (2010) PMID:20551990 Improvement of the enediyne antitumor antibiotic C-1027 production by manipulating its biosynthetic pathway regulation in Streptomyces globisporus. Chen Y et al., J Nat Prod (2011) PMID:21250756 Specificity of the ester bond forming condensation enzyme SgcC5 in C-1027 biosynthesis. Lin S et al., Org Lett (2012) PMID:22519717

Chemical products information

C-1027 [synonyms: lidamycin, c-1027 chromophore]

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C₄₃H₄₂Cl₁N₃O₁₃

Chemical database entries
NPAtlas
PubCHEM

List of genes involved in compound(s) production

Identifiers	Position	Product	Functions	Evidence	Extra
AAL06648.1	8 - 658 (-)	hydroxylase-like protein			copy AA seq copy Nt seq
AAL06649.1	930 - 1478 (-)	viral infectivity potentiator-like protein			copy AA seq copy Nt seq
AAL06650.1	1649 - 2713 (-)	truncated methionine synthase-like protein			copy AA seq copy Nt seq
AAL06651.1	2851 - 3237 (-)	transcription factor			copy AA seq copy Nt seq
AAL06652.1	3442 - 4971 (-)	putative primase			copy AA seq copy Nt seq
AAL06653.1	5982 - 7478 (+)	glycerol phosphate ABC transporter	Transport	Sequence-based prediction	copy AA seq copy Nt seq
AAL06654.1	7573 - 9927 (-)	UvrA-like drug resistance pump	Transport	Sequence-based prediction	copy AA seq copy Nt seq
AAL06655.1	9982 - 11349 (-)	Na/H efflux pump	Transport	Sequence-based prediction	copy AA seq copy Nt seq
AAL06656.1	11351 - 12835 (-)	alkylhalidase	Tailoring (Halogenation)	Activity assay	copy AA seq copy Nt seq
AAL06657.1	13012 - 14079 (+)	dNTP-glucose synthase	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06658.1	14212 - 14643 (-)	C-1027 apoprotein	Resistance/immunity	Activity assay	copy AA seq copy Nt seq
AAL06659.1	14690 - 15922 (-)	amino transferase	Precursor biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AAL06660.1	15919 - 16653 (-)	N-methyl transferase	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06661.1	16653 - 17924 (-)	C-methyl transferase	Precursor biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AAL06662.1	18031 - 19188 (-)	epoxide hydrolase	Tailoring (Hydrolysis)	Activity assay	copy AA seq copy Nt seq
AAL06663.1	19262 - 19924 (-)	anthranilate synthase II	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06664.1	19921 - 21402 (-)	anthranilate synthase I	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06665.1	21419 - 22873 (-)	putative phenylacetyl CoA ligase	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06666.1	22870 - 23541 (-)	hypothetical Fe-S flavoprotein	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06667.1	23561 - 24697 (-)	3-O-acyltransferase	Tailoring (Acylation)	Activity assay	copy AA seq copy Nt seq
AAL06668.1	24981 - 25559 (-)	dNTP-4-keto-6-deoxyglucose epimerase	Precursor biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AAL06669.1	25810 - 27165 (+)	squalene monooxygenase-like protein	Unknown	Sequence-based prediction	copy AA seq copy Nt seq
AAL06670.1	27209 - 28588 (+)	glycosyl transferase	Tailoring (Glycosylation)	Knock-out	copy AA seq copy Nt seq
AAL06671.1	28585 - 29583 (+)	dNTP-glucose dehydratase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
AAL06672.1	29627 - 31192 (+)	transmembrane efflux protein	Transport	Sequence-based prediction	copy AA seq copy Nt seq
AAL06673.1	31275 - 32585 (+)	coenzyme F390 synthase-like protein	Unknown	Sequence-based prediction	copy AA seq copy Nt seq
AAL06674.1	32804 - 34387 (+)	chlorophenol-4-monooxygenase	Tailoring (Hydroxylation)	Activity assay	copy AA seq copy Nt seq
AAL06675.1	34453 - 35289 (-)	haloacetate dehalogenase	Unknown	Sequence-based prediction	copy AA seq copy Nt seq
AAL06676.1	35511 - 35933 (-)	Unknown			copy AA seq copy Nt seq
AAL06677.1	36160 - 37485 (+)	citrate/shikimate transporter	Transport	Sequence-based prediction	copy AA seq copy Nt seq
AAL06678.1	37554 - 38933 (+)	C-domain type II peptide synthetase	Tailoring (Acylation)	Activity assay	copy AA seq copy Nt seq
AAL06679.1	38978 - 39259 (+)	type II PCP	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06680.1	39362 - 40981 (-)	putative ammonia lyase/transferase	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06681.1	41047 - 43692 (-)	A-domain type II peptide synthetase	Precursor biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06682.1	43940 - 46018 (+)	antibiotic transporter	Transport	Sequence-based prediction	copy AA seq copy Nt seq
AAL06683.1	46162 - 47166 (+)	O-methyltransferase	Tailoring (Methylation)	Sequence-based prediction	copy AA seq copy Nt seq
AAL06684.1	47223 - 48479 (+)	P450 hydroxylase	Tailoring (Hydroxylation)	Sequence-based prediction	copy AA seq copy Nt seq
AAL06685.1	48603 - 49709 (-)	oxidoreductase	Unknown	Sequence-based prediction	copy AA seq copy Nt seq
AAL06686.1	50345 - 51385 (+)	Unknown			copy AA seq copy Nt seq
AAL06687.1	51416 - 52336 (-)	oxidoreductase	Unknown	Sequence-based prediction	copy AA seq copy Nt seq
AAL06688.1	53212 - 54069 (+)	Unknown			copy AA seq copy Nt seq
AAL06689.1	54226 - 55374 (+)	Regulator	Regulation	Knock-out	copy AA seq copy Nt seq
AAL06690.1	56021 - 56875 (+)	putative oxidase			copy AA seq copy Nt seq
AAL06691.1	56922 - 57725 (-)	Unknown			copy AA seq copy Nt seq
AAL06692.1	57828 - 58298 (-)	thioesterase	Scaffold biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06693.1	58435 - 60090 (-)	oxidoreductase	Unknown	Sequence-based prediction	copy AA seq copy Nt seq
AAL06694.1	60087 - 60677 (-)	putative regulatory protein			copy AA seq copy Nt seq
AAL06695.1	60935 - 62014 (+)	regulatory protein	Regulation	Other in vivo study	copy AA seq copy Nt seq
AAL06696.1	62040 - 62894 (+)	putative regulatory protein	Regulation	Other in vivo study	copy AA seq copy Nt seq
AAL06697.1	62782 - 64131 (-)	P450 hydroxylase			copy AA seq copy Nt seq
AAL06698.1	64128 - 64676 (-)	oxidoreductase	Unknown	Activity assay	copy AA seq copy Nt seq
AAL06699.1	64757 - 70576 (-)	polyketide synthase	Scaffold biosynthesis	Activity assay	copy AA seq copy Nt seq
AAL06700.1	70573 - 71703 (-)	Unknown			copy AA seq copy Nt seq
AAL06701.1	71700 - 73628 (-)	Unknown			copy AA seq copy Nt seq
AAL06702.1	73625 - 74611 (-)	hypothetical protein			copy AA seq copy Nt seq
AAL06703.1	74942 - 75688 (-)	hypothetical protein			copy AA seq copy Nt seq
AAL06704.1	75873 - 76316 (-)	hypothetical protein	Unknown	Knock-out	copy AA seq copy Nt seq
AAL06705.1	76421 - 77026 (+)	hypothetical protein			copy AA seq copy Nt seq
AAL06706.1	77031 - 77492 (+)	hypothetical protein			copy AA seq copy Nt seq
AAL06707.1	77582 - 78769 (-)	TylR regulatory protein-like protein	Regulation	Other in vivo study	copy AA seq copy Nt seq
AAL06708.1	80060 - 81484 (+)	putative primase/helicase			copy AA seq copy Nt seq
AAL06709.1	81442 - 81855 (-)	unknown			copy AA seq copy Nt seq
AAL06710.1	81881 - 82351 (-)	hypothetical protein			copy AA seq copy Nt seq
AAL06711.1	82408 - 83091 (+)	hypothetical protein			copy AA seq copy Nt seq
AAL06712.1	83115 - 83513 (-)	unknown			copy AA seq copy Nt seq
AAL06713.1	83510 - 85045 (-)	putative primase/helicase-like protein			copy AA seq copy Nt seq

Polyketide-specific information

Subclass	Enediyine
Starter unit	Acetyl-CoA
Cyclic?	yes

Polyketide-synthases

Genes	Properties	Modules
AAL06699.1 + AAL06692.1	Synthase subclass: Iterative type I/Enediyne type I Thioesterases: AAL06692.1 (Type II) Iterative PKS type: Partially reducing, Unknown Iteration counts: 7	Module 1 Specificity: Malonyl-CoA Evidence for specificity: Activity assay Genes: AAL06699.1 Core domains: Ketosynthase, Acyltransferase, Thiolation (ACP/PCP), Ketoreductase, Dehydratase KR-domain stereochemistry: L-OH Non-canonical activity: Iterated Evidence for non-canonical activity: Activity assay

Annotation changelog

MIBiG version	Submitter	Notes
1.0	Hidden contributor (ID: E2T2HCM4X7QXVS4LL4JVBPPK, no GDPR consent given).	Submitted
2.0	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Migrated from v1.4 Updated compound(s) information (NPAtlas curation)
3.0	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Corrected gene identifiers
3.1	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Update chemical activity to schema version 2.11

Detailed domain annotation

Selected features only

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