Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000834.1:
Cluster 1Saccharide / Other123218

BGC0000834, novobiocin biosynthetic gene cluster from Streptomyces niveus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: novobiocin
PubChem ID: 54675769
SMILES string: Copy to clipboard
Molecular formula: C31H36N2O11
Average molecular mass: 612.632 Da
Molecular activity: Antibacterial
Molecular target: GyrB, subunit B protein of DNA gyrase

Class-specific details

Biosynthetic class(es):
Saccharide / Other
Saccharide subclass:
hybrid/tailoring
Glycosyltransferases:
AAF67506.1:
Specificity: L-noviose
Evidence for specificity: Activity assay
Sugar biosynthesis subcluster: AAF67512.1, AAF67513.1, AAF67514.1, AAF67515.1, AAF67516.1
Other biosynthetic class:
Aminocoumarin

Gene cluster description

novobiocin (BGC0000834). Gene Cluster 1. Biosynthetic class = Saccharide/Other. GenBank AF170880, positions 4859-28076. Click on genes for more information.

Legend:

biosynthetic genes
transport-related genes
regulatory genes
other genes

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
MIxS-compliance:Unknown
Contact for this cluster:Alexander Kristian Apel (Eberhard Karls Universitaet Tuebingen)

Literature references

1. Steffensky M et al. (2000) Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891. Antimicrob Agents Chemother 44(5):1214-22.
2. Steffensky M et al. (2000) Cloning, overexpression, and purification of novobiocic acid synthetase from Streptomyces spheroides NCIMB 11891. J Biol Chem 275(28):21754-60. doi: 10.1074/jbc.M003066200.
3. Xu H et al. (2002) Genetic analysis of the biosynthesis of the pyrrole and carbamoyl moieties of coumermycin A1 and novobiocin. Mol Genet Genomics 268(3):387-96. doi: 10.1007/s00438-002-0759-1. Epub
4. Eustaquio AS et al. (2003) Novobiocin biosynthesis: inactivation of the putative regulatory gene novE and heterologous expression of genes involved in aminocoumarin ring formation. Arch Microbiol 180(1):25-32. doi: 10.1007/s00203-003-0555-2. Epub 2003
5. Freel Meyers CL et al. (2004) Characterization of NovP and NovN: completion of novobiocin biosynthesis by sequential tailoring of the noviosyl ring. Angew Chem Int Ed Engl 43(1):67-70. doi: 10.1002/anie.200352626.
6. Keller S et al. (2006) Molecular replacement in the 'twilight zone': structure determination of the non-haem iron oxygenase NovR from Streptomyces spheroides through repeated density modification of a poor molecular-replacement solution. Acta Crystallogr D Biol Crystallogr 62(Pt 12):1564-70. doi:
7. Eustaquio AS et al. (2005) NovG, a DNA-binding protein acting as a positive regulator of novobiocin biosynthesis. Microbiology 151(Pt 6):1949-61. doi: 10.1099/mic.0.27669-0.
8. Eustaquio AS et al. (2005) Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters. Appl Environ Microbiol 71(5):2452-9. doi:
9. Thuy TT et al. (2005) Functional characterizations of novWUS involved in novobiocin biosynthesis from Streptomyces spheroides. Arch Biochem Biophys 436(1):161-7. doi: 10.1016/j.abb.2005.01.012.
10. Flinspach K et al. (2014) Draft Genome Sequence of Streptomyces niveus NCIMB 11891, Producer of the Aminocoumarin Antibiotic Novobiocin. LID - 10.1128/genomeA.01146-13 [doi] LID - e01146-13 [pii] Genome Announc 2(1). pii: 2/1/e01146-13. doi:
11. Dangel V et al. (2009) Transcriptional regulation of the novobiocin biosynthetic gene cluster. Microbiology 155(Pt 12):4025-35. doi: 10.1099/mic.0.032649-0. Epub 2009
12. Dangel V et al. (2008) novE and novG act as positive regulators of novobiocin biosynthesis. Arch Microbiol 190(5):509-19. doi: 10.1007/s00203-008-0396-0. Epub 2008
13. Gomez Garcia I et al. (2008) Crystallization and preliminary X-ray analysis of the O-carbamoyltransferase NovN from the novobiocin-biosynthetic cluster of Streptomyces spheroides. Acta Crystallogr Sect F Struct Biol Cryst Commun 64(Pt 11):1000-2.
14. Gomez Garcia I et al. (2010) The crystal structure of the novobiocin biosynthetic enzyme NovP: the first representative structure for the TylF O-methyltransferase superfamily. J Mol Biol 395(2):390-407. doi: 10.1016/j.jmb.2009.10.045. Epub 2009
15. Stevenson CE et al. (2007) Crystallization and preliminary X-ray analysis of the O-methyltransferase NovP from the novobiocin-biosynthetic cluster of Streptomyces spheroides. Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 3):236-8. doi:
16. Tello M et al. (2006) Characterisation of Streptomyces spheroides NovW and revision of its functional assignment to a dTDP-6-deoxy-D-xylo-4-hexulose 3-epimerase. Chem Commun (Camb) (10):1079-81. doi: 10.1039/b515763c. Epub 2006
17. Jakimowicz P et al. (2006) The 1.6-A resolution crystal structure of NovW: a 4-keto-6-deoxy sugar epimerase from the novobiocin biosynthetic gene cluster of Streptomyces spheroides. Proteins 63(1):261-5. doi: 10.1002/prot.20818.
18. Pacholec M et al. (2005) CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry 44(45):14969-76. doi: 10.1021/bi051599o.
19. Pacholec M et al. (2005) NovJ/NovK catalyze benzylic oxidation of a beta-hydroxyl tyrosyl-S-pantetheinyl enzyme during aminocoumarin ring formation in novobiocin biosynthesis. Biochemistry 44(38):12819-26. doi: 10.1021/bi051297m.
20. Freel Meyers CL et al. (2004) Characterization of NovP and NovN: completion of novobiocin biosynthesis by sequential tailoring of the noviosyl ring. Angew Chem Int Ed Engl 43(1):67-70. doi: 10.1002/anie.200352626.
21. Jakimowicz P et al. (2003) Crystallization and preliminary X-ray studies on the putative dTDP sugar epimerase NovW from the novobiocin biosynthetic cluster of Streptomyces spheroides. Acta Crystallogr D Biol Crystallogr 59(Pt 8):1507-9. Epub 2003 Jul 23.
22. Freel Meyers CL et al. (2003) Initial characterization of novobiocic acid noviosyl transferase activity of NovM in biosynthesis of the antibiotic novobiocin. Biochemistry 42(14):4179-89. doi: 10.1021/bi0340088.
23. Chen H, Walsh CT. (2001) Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI. Chem Biol 8(4):301-12.
24. HARRIS DA et al. (1955-1956 TI) Discovery and antimicrobial properties of cathomycin, a new antibiotic produced by Streptomyces spheroides n. sp. Antibiot Annu 3:909-17.
25. CUCKLER AC et al. (1955-1956 TI) The antimicrobial activity of cathomycin, a new antibiotic. Antibiot Annu 3:918-23.
26. Ozaki T et al. (2009) NovQ is a prenyltransferase capable of catalyzing the addition of a dimethylallyl group to both phenylpropanoids and flavonoids. J Antibiot (Tokyo) 62(7):385-92. doi: 10.1038/ja.2009.48. Epub 2009 Jun
27. SMITH CG et al. (1956) Streptonivicin, a new antibiotic. I. Discovery and biologic studies. Antibiot Chemother (Northfield) 6(2):135-42.