BGC0000247

BGC0000247: mithramycin biosynthetic gene cluster from Streptomyces argillaceus

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Location: 1 - 42,374 nt. (total: 42,374 nt).
This entry is originally from NCBI GenBank X89899.2.

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core biosynthetic genes

additional biosynthetic genes

transport-related genes

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Gene details

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General

Compounds

Genes

Polyketide

Saccharide

History

NRPS/PKS domains

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General information about the BGC

MIBiG accession	BGC0000247
Short description	mithramycin biosynthetic gene cluster from Streptomyces argillaceus
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 (Other) Saccharide (oligosaccharide)
Loci	NCBI GenBank: X89899.2
Compounds	mithramycin
Species	Streptomyces argillaceus [taxonomy]
References	Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin. Lombó F et al., Gene (1996) PMID:8654997 Cloning and insertional inactivation of Streptomyces argillaceus genes involved in the earliest steps of biosynthesis of the sugar moieties of the antitumor polyketide mithramycin. Lombó F et al., J Bacteriol (1997) PMID:9150235 Analysis of two chromosomal regions adjacent to genes for a type II polyketide synthase involved in the biosynthesis of the antitumor polyketide mithramycin in Streptomyces argillaceus. Prado L et al., Mol Gen Genet (1999) PMID:10102355 The mtmVUC genes of the mithramycin gene cluster in Streptomyces argillaceus are involved in the biosynthesis of the sugar moieties. González A et al., Mol Gen Genet (2001) PMID:11254130 Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents. Blanco G et al., Chem Biol (1996) PMID:8807845 An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producer Streptomyces argillaceus. Fernández E et al., Mol Gen Genet (1996) PMID:8757400 Folding of the polyketide chain is not dictated by minimal polyketide synthase in the biosynthesis of mithramycin and anthracycline. Kantola J et al., Chem Biol (1997) PMID:9375253 Identification of two genes from Streptomyces argillaceus encoding glycosyltransferases involved in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin. Fernández E et al., J Bacteriol (1998) PMID:9733697 The mithramycin gene cluster of Streptomyces argillaceus contains a positive regulatory gene and two repeated DNA sequences that are located at both ends of the cluster. Lombó F et al., J Bacteriol (1999) PMID:9882681 Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin. Prado L et al., Chem Biol (1999) PMID:9889148 The structure of mithramycin reinvestigated. Wohlert SE et al., J Nat Prod (1999) PMID:9917296 Characterization of two glycosyltransferases involved in early glycosylation steps during biosynthesis of the antitumor polyketide mithramycin by Streptomyces argillaceus. Blanco G et al., Mol Gen Genet (2000) PMID:10660060 The Novel Hybrid Antitumor Compound Premithramycinone H Provides Indirect Evidence for a Tricyclic Intermediate of the Biosynthesis of the Aureolic Acid Antibiotic Mithramycin. Lombó F et al., Angew Chem Int Ed Engl (2000) PMID:10760873 Characterization of two polyketide methyltransferases involved in the biosynthesis of the antitumor drug mithramycin by Streptomyces argillaceus. Lozano MJ et al., J Biol Chem (2000) PMID:10652287 Insertional inactivation of mtrX and mtrY genes from the mithramycin gene cluster affects production and growth of the producer organism Streptomyces argillaceus. Garcia-Bernardo J et al., FEMS Microbiol Lett (2000) PMID:10779713 Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel insights into post-PKS tailoring steps of the mithramycin biosynthetic pathway. Remsing LL et al., J Am Chem Soc (2002) PMID:11853433 Rationally designed glycosylated premithramycins: hybrid aromatic polyketides using genes from three different biosynthetic pathways. Trefzer A et al., J Am Chem Soc (2002) PMID:12022840 Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus through combinatorial biosynthesis. Remsing LL et al., J Am Chem Soc (2003) PMID:12733914 Purification and characterization of a monooxygenase involved in the biosynthetic pathway of the antitumor drug mithramycin. Rodríguez D et al., J Bacteriol (2003) PMID:12813091 MtmMII-mediated C-methylation during biosynthesis of the antitumor drug mithramycin is essential for biological activity and DNA-drug interaction. Rodríguez D et al., J Biol Chem (2004) PMID:14660589 Elucidation of the glycosylation sequence of mithramycin biosynthesis: isolation of 3A-deolivosylpremithramycin B and its conversion to premithramycin B by glycosyltransferase MtmGII. Nur-e-Alam M et al., Chembiochem (2005) PMID:15712316

Chemical products information

mithramycin [synonyms: Aureolic Acid, Mitramycin, Plicamycin]

Copy SMILES

C₅₂H₇₆O₂₄

List of genes involved in compound(s) production

Identifiers	Position	Product	Functions	Evidence	Extra
CAK50769.1	218 - 1462 (-)	membrane protein			copy AA seq copy Nt seq
CAK50770.1 mtmR	3416 - 4246 (+)	mithramycin regulator MtmR	Regulation	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50771.1 mtmZ	4347 - 5129 (+)	putative thioesterase			copy AA seq copy Nt seq
CAK50772.1 mtmA	5258 - 6640 (+)	AdoMet synthetase and MTHF reductase fusion			copy AA seq copy Nt seq
CAK50773.1 mtmH	6630 - 8078 (+)	adoHcyase			copy AA seq copy Nt seq
CAK50774.1 mtmD	8142 - 9209 (+)	dTDP-glucose synthase	Tailoring (Unknown)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50775.1 mtmE	9206 - 10201 (+)	dTDP-glucose 4,6-dehydratase			copy AA seq copy Nt seq
CAK50776.1 mtmTII	10620 - 11381 (-)	ketoreductase			copy AA seq copy Nt seq
CAK50777.1 mtmOII	11398 - 12993 (-)	oxygenase	Tailoring (Hydroxylation)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50778.1 mtmOIII	12986 - 13285 (-)	oxygenase			copy AA seq copy Nt seq
CAK50779.1 mtmL	13329 - 14873 (-)	acyl CoA ligase			copy AA seq copy Nt seq
CAA61987.1 mtmQ	14866 - 15813 (-)	aromatase			copy AA seq copy Nt seq
CAA61988.1 mtmX	16025 - 16477 (+)	cyclase			copy AA seq copy Nt seq
CAA61989.1 mtmP	16658 - 17926 (+)	ketoacyl synthase	Scaffold biosynthesis	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAA61990.1 mtmK	17923 - 19149 (+)	mtmK protein			copy AA seq copy Nt seq
CAA61991.1 mtmS	19209 - 19466 (+)	acyl carrier protein			copy AA seq copy Nt seq
CAK50780.1 mtmTI	19497 - 20261 (+)	ketoreductase			copy AA seq copy Nt seq
CAK50781.1 mtmOI	20265 - 21575 (+)	oxygenase			copy AA seq copy Nt seq
CAK50782.1 mtmY	21579 - 22352 (+)	cyclase			copy AA seq copy Nt seq
CAK50783.1 mtmTIII	22425 - 23168 (-)	ketoreductase	Tailoring (Unknown)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50784.1 mtmC	23171 - 24436 (-)	D-mycarose 3-C-methyltransferase and 4-D-olivosyl-ketoreductase	Scaffold biosynthesis	Activity assay Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50785.1 mtmU	24466 - 25452 (-)	D-oliose 4-ketoreductase	Tailoring (Unknown)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50786.1 mtmV	25458 - 26918 (-)	D-olivose, D-oliose and D-mycarose 2,3-dehydratase	Tailoring (Unknown)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50787.1 mtmW	27067 - 28047 (+)	putative side chain reductase	Tailoring (Reduction)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50788.1 mtmGIV	28338 - 29561 (+)	glycosyltransferase	Tailoring (Glycosylation)	Activity assay Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50789.1 mtmGIII	29634 - 30824 (+)	glycosyltransferase	Tailoring (Glycosylation)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50790.1 mtmMII	30885 - 31865 (+)	C-methyltransferase	Tailoring (Methylation)	Activity assay Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50791.1 mtmMI	31928 - 32965 (+)	O-methyltransferase	Tailoring (Methylation)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50792.1 mtmGII	33114 - 34253 (-)	glycosyltransferase	Tailoring (Glycosylation)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50793.1 mtmGI	34474 - 35655 (+)	glycosyltransferase	Tailoring (Glycosylation)	Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50794.2 mtmOIV	35655 - 37256 (+)	oxygenase	Tailoring (Hydroxylation)	Activity assay Knock-out Sequence-based prediction	copy AA seq copy Nt seq
CAK50795.1 mtrX	37327 - 39813 (+)	MtrX			copy AA seq copy Nt seq
CAK50796.1 mtrY	39841 - 40500 (+)	MtrY protein			copy AA seq copy Nt seq
CAK50797.1 mtrA	40562 - 41524 (+)				copy AA seq copy Nt seq
CAK50798.1 mtrB	41587 - 42288 (+)				copy AA seq copy Nt seq

Polyketide-specific information

Subclass	Other
Starter unit	Malonyl-CoA
Ketide length	10
Cyclic?	yes

Polyketide-synthases

Genes	Properties	Modules
mtmX + mtmS + mtmY + mtmQ + mtmP	Synthase subclass: Type II

Saccharide-specific information

Subclass	oligosaccharide
Glycosyltransferases	mtmGIV Specificity: D-olivose Evidence: Activity assay
	mtmGIV Specificity: D-mycarose Evidence: Activity assay
	mtmGIII Specificity: D-oliose Evidence: Knock-out construct
	mtmGII Specificity: D-olivose Evidence: Knock-out construct
	mtmGI Specificity: D-olivose Evidence: Knock-out construct

Annotation changelog

MIBiG version	Submitter	Notes
1.0	Hidden contributor (ID: IROSGRAECON7XFWB774QFHDN, no GDPR consent given).	Submitted
2.0	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Migrated from v1.4
3.0	Hidden contributor (ID: 3UOU7PODQJXIM6BEPUHHRRA5, no GDPR consent given). Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Remove duplicated citations Updated bioactivity data
3.1	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Update chemical activity to schema version 2.11

Detailed domain annotation

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