BGC0000055

General information about the BGC

MIBiG accession	BGC0000055
Short description	erythromycin A biosynthetic gene cluster from Saccharopolyspora erythraea NRRL 2338
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 (Macrolide) Saccharide (hybrid/tailoring)
Loci	NCBI GenBank: AM420293.1
Compounds	erythromycin A erythromycin B erythromycin C erythromycin D
Species	Saccharopolyspora erythraea NRRL 2338 [taxonomy]
References	Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis). Rawlings BJ, Nat Prod Rep (2001) PMID:11336289 Architectures of whole-module and bimodular proteins from the 6-deoxyerythronolide B synthase. Edwards AL et al., J Mol Biol (2014) PMID:24704088 Systems perspectives on erythromycin biosynthesis by comparative genomic and transcriptomic analyses of S. erythraea E3 and NRRL23338 strains. Li YY et al., BMC Genomics (2013) PMID:23902230 Knocking out of tailoring genes eryK and eryG in an industrial erythromycin-producing strain of Saccharopolyspora erythraea leading to overproduction of erythromycin B, C and D at different conversion ratios. Zhang Q et al., Lett Appl Microbiol (2011) PMID:21175699 Knockout of the erythromycin biosynthetic cluster gene, eryBI, blocks isoflavone glucoside bioconversion during erythromycin fermentations in Aeromicrobium erythreum but not in Saccharopolyspora erythraea. Reeves AR et al., Appl Environ Microbiol (2008) PMID:18836015 Genetic modulation of the overexpression of tailoring genes eryK and eryG leading to the improvement of erythromycin A purity and production in Saccharopolyspora erythraea fermentation. Chen Y et al., Appl Environ Microbiol (2008) PMID:18223111 Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338. Oliynyk M et al., Nat Biotechnol (2007) PMID:17369815 Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea. Reeves AR et al., J Ind Microbiol Biotechnol (2006) PMID:16491356 Improved bioconversion of 15-fluoro-6-deoxyerythronolide B to 15-fluoro-erythromycin A by overexpression of the eryK Gene in Saccharopolyspora erythraea. Desai RP et al., Biotechnol Prog (2004 Nov-Dec) PMID:15575696 Reconstitution and characterization of a new desosaminyl transferase, EryCIII, from the erythromycin biosynthetic pathway. Lee HY et al., J Am Chem Soc (2004) PMID:15303858 A specific role of the Saccharopolyspora erythraea thioesterase II gene in the function of modular polyketide synthases. Hu Z et al., Microbiology (Reading) (2003) PMID:12904561 Analysis of an 8.1-kb DNA fragment contiguous with the erythromycin gene cluster of Saccharopolyspora erythraea in the eryCI-flanking region. Reeves AR et al., Antimicrob Agents Chemother (2002) PMID:12435693 Transcriptional organization of the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea. Reeves AR et al., J Bacteriol (1999) PMID:10559177 Analysis of eryBI, eryBIII and eryBVII from the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea. Gaisser S et al., Mol Gen Genet (1998) PMID:9613575 Targeted gene inactivation for the elucidation of deoxysugar biosynthesis in the erythromycin producer Saccharopolyspora erythraea. Salah-Bey K et al., Mol Gen Genet (1998) PMID:9563840 The loading domain of the erythromycin polyketide synthase is not essential for erythromycin biosynthesis in Saccharopolyspora erythraea. Pereda A et al., Microbiology (Reading) (1998) PMID:9493390 Analysis of seven genes from the eryAI-eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea. Gaisser S et al., Mol Gen Genet (1997) PMID:9393448 Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production. Summers RG et al., Microbiology (Reading) (1997) PMID:9353926 Cloning and heterologous expression of the genes encoding nonspecific electron transport components for a cytochrome P450 system of Saccharopolyspora erythraea involved in erythromycin production. Zotchev SB et al., Gene (1995) PMID:7737500 Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Cupp-Vickery JR et al., Nat Struct Biol (1995) PMID:7749919 Inhibition of erythromycin synthesis by disruption of malonyl-coenzyme A decarboxylase gene eryM in Saccharopolyspora erythraea. Hsieh YJ et al., J Bacteriol (1994) PMID:8300527 Substrate specificity of 6-deoxyerythronolide B hydroxylase, a bacterial cytochrome P450 of erythromycin A biosynthesis. Andersen JF et al., Biochemistry (1993) PMID:8448148 6-Deoxyerythronolide B synthase 3 from Saccharopolyspora erythraea: over-expression in Escherichia coli, purification and characterisation. Roberts GA et al., Biochem Soc Trans (1993) PMID:8449313 Identification of a Saccharopolyspora erythraea gene required for the final hydroxylation step in erythromycin biosynthesis. Stassi D et al., J Bacteriol (1993) PMID:8416893 Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea. Caffrey P et al., FEBS Lett (1992) PMID:1618327 Cloning and sequence analysis of genes involved in erythromycin biosynthesis in Saccharopolyspora erythraea: sequence similarities between EryG and a family of S-adenosylmethionine-dependent methyltransferases. Haydock SF et al., Mol Gen Genet (1991) PMID:1840640 An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Cortes J et al., Nature (1990) PMID:2234082 Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea. Weber JM et al., J Bacteriol (1990) PMID:2185216 Cloning of genes governing the deoxysugar portion of the erythromycin biosynthesis pathway in Saccharopolyspora erythraea (Streptomyces erythreus). Vara J et al., J Bacteriol (1989) PMID:2681144 Molecular characterization of a gene from Saccharopolyspora erythraea (Streptomyces erythraeus) which is involved in erythromycin biosynthesis. Dhillon N et al., Mol Microbiol (1989) PMID:2575703 Identification of a gene required for the terminal step in erythromycin A biosynthesis in Saccharopolyspora erythraea (Streptomyces erythreus). Weber JM et al., Gene (1989) PMID:2469627

Chemical products information

erythromycin A [synonyms: abomacetin, erythromycin]

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C₃₇H₆₇N₁O₁₃

Chemical database entries
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ChEBI
ChEMBL
ChemSpider

erythromycin B [synonyms: berythromycin]

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C₃₇H₆₇N₁O₁₂

Chemical database entries
NPAtlas
PubCHEM
ChEBI
ChEMBL
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erythromycin C

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C₃₆H₆₅N₁O₁₃

Chemical database entries
NPAtlas
PubCHEM
ChEBI
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erythromycin D

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C₃₆H₆₅N₁O₁₂

Chemical database entries
PubCHEM
ChEBI
ChemSpider

List of genes involved in compound(s) production

Identifiers	Position	Product	Functions	Evidence	Extra
SACE_0712 CAM00053.1	778214 - 778594 (+)	putative erythromycin esterase			copy AA seq copy Nt seq
SACE_0713 CAM00054.1 eryK	778654 - 779847 (+)	cytochrome P450 Erythromycin B/D C-12 hydroxylase	Tailoring (Hydroxylation)	Activity assay Knock-out	copy AA seq copy Nt seq
SACE_0714 CAM00055.1 eryBVII	779802 - 780404 (-)	dTDP-4-deoxyglucose 3,5-epimerase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0715 CAM00056.1 eryCV	780412 - 781881 (-)	EryCV NDP-4,6-dideoxyhexose 3,4-enoyl reductase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0716 CAM00057.1 eryCIV	781919 - 783124 (-)	eryCIV NDP-6-deoxyhexose 3,4-dehydratase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0717 CAM00058.1 eryBVI	783121 - 784584 (-)	NDP-4-keto-6-deoxy-glucose 2,3-dehydratase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0718 CAM00059.1 eryCVI	784738 - 785451 (-)	TDP-desosamine-N-dimethyltransferase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0719 CAM00060.1 eryBV	785504 - 786751 (-)	6-DEB TDP-mycarosyl glycosyltransferase	Tailoring (Glycosylation)	Knock-out	copy AA seq copy Nt seq
SACE_0720 CAM00061.1 eryBIV	786751 - 787719 (-)	dTDP-4-keto-6-deoxy-L-hexose 4-reductase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0721 CAM00062.1 eryAI	787944 - 798581 (+)	EryAI Erythromycin polyketide synthase modules 1 and 2	Scaffold biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0722 CAM00063.1	798638 - 799849 (-)	transposase			copy AA seq copy Nt seq
SACE_0723 CAM00064.1 eryAII	800023 - 810726 (+)	EryAII Erythromycin polyketide synthase modules 3 and 4	Scaffold biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0724 CAM00065.1 eryAIII	810727 - 820242 (+)	EryAIII Erythromycin polyketide synthase modules 5 and 6	Scaffold biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0725 CAM00066.1 eryCII	820239 - 821324 (+)	TDP-4-keto-6-deoxy-glucose 3,4-isomerase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0726 CAM00067.1 eryCIII	821335 - 822600 (+)	glycosyl transferase, NDP-D-desosamine : 3-L-mycarosyl erythronolide B	Tailoring (Glycosylation)	Knock-out	copy AA seq copy Nt seq
SACE_0727 CAM00068.1 eryBII	822597 - 823598 (+)	TDP-4-keto-6-deoxyhexose 2,3-reductase	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq
SACE_0728 CAM00069.1 eryG	823630 - 824550 (+)	erythromycin C methlytransferase	Tailoring (Methylation)	Knock-out	copy AA seq copy Nt seq
SACE_0729 CAM00070.1	824527 - 825270 (-)	thioesterase, erythromycin biosynthesis	Activation / processing	Other in vivo study	copy AA seq copy Nt seq
SACE_0730 CAM00071.1 eryF	825267 - 826481 (-)	6-deoxyerythronolide B hydroxylase (6-DEB hydroxylase)	Tailoring (Hydroxylation)	Knock-out	copy AA seq copy Nt seq
SACE_0731 CAM00072.1 eryBIII	826478 - 827710 (-)	eryBIII NDP-4-keto-2,6-dideoxyhexose 3-C-methyltransferase	Precursor biosynthesis	Other in vivo study	copy AA seq copy Nt seq
SACE_0732 CAM00073.1 eryBI	827912 - 830338 (+)	beta-D-glucosidase			copy AA seq copy Nt seq
SACE_0733 CAM00074.1 ermE	830393 - 831538 (-)	N-6-aminoadenine-N-methyltransferase, erythromycinresistance	Resistance/immunity	Other in vivo study	copy AA seq copy Nt seq
SACE_0734 CAM00075.1 eryCI	831725 - 832825 (+)	Erythromycin biosynthesis transaminase EryCI	Precursor biosynthesis	Knock-out	copy AA seq copy Nt seq

Polyketide-specific information

Subclass	Macrolide
Starter unit	Propionyl-CoA
Cyclic?	yes
Release type	Macrolactonization

Polyketide-synthases

Genes	Properties	Modules
eryAII + SACE_0729 + eryAIII + eryAI	Synthase subclass: Modular type I Thioesterases: SACE_0729 (Unknown)	Module 0 Specificity: Propionyl-CoA Evidence for specificity: Structure-based inference Genes: eryAI Core domains: Acyltransferase, Thiolation (ACP/PCP)
		Module 1 Specificity: Methylmalonyl-CoA Evidence for specificity: Structure-based inference Genes: eryAI Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: D-OH
		Module 2 Specificity: Methylmalonyl-CoA Evidence for specificity: Structure-based inference Genes: eryAI Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: L-OH
		Module 3 Specificity: Methylmalonyl-CoA Evidence for specificity: Structure-based inference Genes: eryAII Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: Inactive
		Module 4 Specificity: Methylmalonyl-CoA Evidence for specificity: Structure-based inference Genes: eryAII Core domains: Ketosynthase, Acyltransferase, Dehydratase, Enoylreductase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: Unknown
		Module 5 Specificity: Methylmalonyl-CoA Evidence for specificity: Structure-based inference Genes: eryAIII Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: L-OH
		Module 6 Specificity: Methylmalonyl-CoA Evidence for specificity: Structure-based inference Genes: eryAIII Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Thiolation (ACP/PCP), Thioesterase KR-domain stereochemistry: L-OH

Saccharide-specific information

Subclass	hybrid/tailoring
Sugar-encoding genes	eryCII, eryCIV, eryCV, eryCVI eryBII, eryBIV, eryBVI, eryBVII
Glycosyltransferases	eryCIII Specificity: D-desosamine Evidence: Activity assay
Glycosyltransferases	eryBV Specificity: L-mycarose Evidence: Activity assay

Annotation changelog

MIBiG version	Submitter	Notes
1.0	Hidden contributor (ID: AK53UXEU2X7JUZMX7VY3GZAO, 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).	Removed ketoreductase stereochemistry annotation from modules without ketoreductases
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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Similar known gene clusters

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