Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000055.1:
Cluster 1Polyketide / Saccharide154612

BGC0000055, erythromycin biosynthetic gene cluster from Saccharopolyspora erythraea. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: Erythromycin A
PubChem ID: 12560
ChEBI ID: 42355
ChEMBL ID: 532
ChemSpider ID: 12041
SMILES string: Copy to clipboard
Molecular formula: C37H67NO13
Average molecular mass: 733.92678 Da
Molecular activity: Antibacterial, Inhibitor
Molecular target: Bacterial 70S ribosome

Class-specific details

Biosynthetic class(es):
Polyketide / Saccharide
Polyketide subclass:
Macrolide (cyclic)
Polyketide synthase subclass:
Modular type I
Starter unit:
Propionyl-CoA
Thioesterase type:
Type I & II
Release / cyclization type:
Macrolactonization

Modular polyketide synthases:
eryAI (CAM00062.1)
Module 0
AT specificity: Propionyl-CoA
Evidence for specificity: Structure-based inference
Scaffold-modifying domain: None
Module 1
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: D-OH
Scaffold-modifying domain: None
Module 2
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: L-OH
Scaffold-modifying domain: None

eryAII (CAM00064.1)
Module 3
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: Inactive
Scaffold-modifying domain: None
Module 4
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: Unknown
Scaffold-modifying domain: None

eryAIII (CAM00065.1)
Module 5
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: L-OH
Scaffold-modifying domain: None
Module 6
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: L-OH
Scaffold-modifying domain: None

Saccharide subclass:
hybrid/tailoring
Glycosyltransferases:
SACE_0726:
Specificity: D-desosamine
Evidence for specificity: Activity assay
Sugar biosynthesis subcluster: SACE_0725,SACE_0716,SACE_0715,SACE_0718
SACE_0719:
Specificity: L-mycarose
Evidence for specificity: Activity assay
Sugar biosynthesis subcluster: SACE_0727,SACE_0720,SACE_0717,SACE_0714

Gene cluster description

erythromycin (BGC0000055). Gene Cluster 1. Biosynthetic class = Polyketide/Saccharide. GenBank AM420293, positions 778214-832825. Click on genes for more information.

Legend:

biosynthetic genes
transport-related genes
regulatory genes
other genes

Domain annotation

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. Rawlings BJ. (2001) Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis). Nat Prod Rep 18(2):190-227.
2. Edwards AL et al. (2014) Architectures of whole-module and bimodular proteins from the 6-deoxyerythronolide B synthase. J Mol Biol 426(11):2229-45. doi: 10.1016/j.jmb.2014.03.015. Epub
3. Li YY et al. (2013 TI) Systems perspectives on erythromycin biosynthesis by comparative genomic and transcriptomic analyses of S. erythraea E3 and NRRL23338 strains. BMC Genomics 14:523. doi: 10.1186/1471-2164-14-523.
4. Zhang Q et al. (2011) 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. Lett Appl Microbiol 52(2):129-37. doi:
5. Reeves AR et al. (2008) Knockout of the erythromycin biosynthetic cluster gene, eryBI, blocks isoflavone glucoside bioconversion during erythromycin fermentations in Aeromicrobium erythreum but not in Saccharopolyspora erythraea. Appl Environ Microbiol 74(23):7383-90. doi: 10.1128/AEM.01759-08. Epub
6. Chen Y et al. (2008) 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. Appl Environ Microbiol 74(6):1820-8. doi: 10.1128/AEM.02770-07. Epub
7. Oliynyk M et al. (2007) Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338. Nat Biotechnol 25(4):447-53. Epub 2007 Mar 18.
8. Reeves AR et al. (2006) Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea. J Ind Microbiol Biotechnol 33(7):600-9. Epub 2006 Feb 21.
9. Desai RP et al. (2004) Improved bioconversion of 15-fluoro-6-deoxyerythronolide B to 15-fluoro-erythromycin A by overexpression of the eryK Gene in Saccharopolyspora erythraea. Biotechnol Prog 20(6):1660-5.
10. Lee HY et al. (2004) Reconstitution and characterization of a new desosaminyl transferase, EryCIII, from the erythromycin biosynthetic pathway. J Am Chem Soc 126(32):9924-5.
11. Hu Z et al. (2003) A specific role of the Saccharopolyspora erythraea thioesterase II gene in the function of modular polyketide synthases. Microbiology 149(Pt 8):2213-25.
12. Reeves AR et al. (2002) Analysis of an 8.1-kb DNA fragment contiguous with the erythromycin gene cluster of Saccharopolyspora erythraea in the eryCI-flanking region. Antimicrob Agents Chemother 46(12):3892-9.
13. Reeves AR et al. (1999) Transcriptional organization of the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea. J Bacteriol 181(22):7098-106.
14. Gaisser S et al. (1998) Analysis of eryBI, eryBIII and eryBVII from the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea. Mol Gen Genet 258(1-2):78-88.
15. Salah-Bey K et al. (1998) Targeted gene inactivation for the elucidation of deoxysugar biosynthesis in the erythromycin producer Saccharopolyspora erythraea. Mol Gen Genet 257(5):542-53.
16. Pereda A et al. (1998) The loading domain of the erythromycin polyketide synthase is not essential for erythromycin biosynthesis in Saccharopolyspora erythraea. Microbiology 144 ( Pt 2):543-53.
17. Gaisser S et al. (1997) Analysis of seven genes from the eryAI-eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea. Mol Gen Genet 256(3):239-51.
18. Summers RG et al. (1997) Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production. Microbiology 143 ( Pt 10):3251-62.
19. Zotchev SB, Hutchinson CR. (1995) Cloning and heterologous expression of the genes encoding nonspecific electron transport components for a cytochrome P450 system of Saccharopolyspora erythraea involved in erythromycin production. Gene 156(1):101-6.
20. Cupp-Vickery JR, Poulos TL. (1995) Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Nat Struct Biol 2(2):144-53.
21. Hsieh YJ, Kolattukudy PE. (1994) Inhibition of erythromycin synthesis by disruption of malonyl-coenzyme A decarboxylase gene eryM in Saccharopolyspora erythraea. J Bacteriol 176(3):714-24.
22. Andersen JF et al. (1993) Substrate specificity of 6-deoxyerythronolide B hydroxylase, a bacterial cytochrome P450 of erythromycin A biosynthesis. Biochemistry 32(8):1905-13.
23. Roberts GA et al. (1993) 6-Deoxyerythronolide B synthase 3 from Saccharopolyspora erythraea: over-expression in Escherichia coli, purification and characterisation. Biochem Soc Trans 21(1):32S.
24. Stassi D et al. (1993) Identification of a Saccharopolyspora erythraea gene required for the final hydroxylation step in erythromycin biosynthesis. J Bacteriol 175(1):182-9.
25. Caffrey P et al. (1992) Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea. FEBS Lett 304(2-3):225-8.
26. Haydock SF et al. (1991) 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. Mol Gen Genet 230(1-2):120-8.
27. Cortes J et al. (1990) An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 348(6297):176-8.
28. Weber JM et al. (1990) Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea. J Bacteriol 172(5):2372-83.
29. Vara J et al. (1989) Cloning of genes governing the deoxysugar portion of the erythromycin biosynthesis pathway in Saccharopolyspora erythraea (Streptomyces erythreus). J Bacteriol 171(11):5872-81.
30. Dhillon N et al. (1989) Molecular characterization of a gene from Saccharopolyspora erythraea (Streptomyces erythraeus) which is involved in erythromycin biosynthesis. Mol Microbiol 3(10):1405-14.
31. Weber JM et al. (1989) Identification of a gene required for the terminal step in erythromycin A biosynthesis in Saccharopolyspora erythraea (Streptomyces erythreus). Gene 75(2):235-41.