Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000024.1:
Cluster 1Polyketide129132

BGC0000024, aureothin biosynthetic gene cluster from Streptomyces thioluteus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: aureothin
PubChem ID: 6436188
ChemSpider ID: 5029106
SMILES string: Copy to clipboard
Molecular formula: C22H23NO6
Average molecular mass: 397.427 Da
Molecular activity: Antibacterial, Antifungal, Cytotoxic, Other

Class-specific details

Biosynthetic class(es):
Polyketide
Polyketide subclass:
Polyene (linear)
Polyketide synthase subclass:
Modular type I
Starter unit:
p-Nitrobenzoate
Thioesterase type:
Type I
Release / cyclization type:
Macrolactamization

Modular polyketide synthases:
aurA (CAE02602.1)
Module 1
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Other
KR stereochemistry: B-group
Module is iterated
Evidence for iteration: Unknown

aurB (CAE02605.1)
Module 2
AT specificity: Malonyl-CoA
Evidence for specificity: Sequence-based prediction
KR stereochemistry: B-group

aurC (CAE02606.1)
Module 3
AT specificity: Methylmalonyl-CoA
Evidence for specificity: Sequence-based prediction
Module 4

Gene cluster description

aureothin (BGC0000024). Gene Cluster 1. Biosynthetic class = Polyketide. GenBank AJ575648. 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, Sequence-based prediction
MIxS-compliance:Unknown
Contact for this cluster:Keishi Ishida (Leipniz Institute for Natural Product Research and Infection Biology)

Literature references

1. WASHIZU F et al. (1954) Chemical studies on a toxic product of Streptomyces thioluteus, aureothin. J Antibiot (Tokyo) 7(2):60.
2. Schwartz JL et al. (1976) Identification of mycolutein and pulvomycin as aureothin and labilomycin respectively. J Antibiot (Tokyo) 29(3):236-41.
3. Taniguchi M et al. (2000) Gamma-pyrone compounds with selective and potent anti-Helicobacter pylori activity. J Antibiot (Tokyo) 53(8):844-7.
4. He J, Hertweck C. (2003) Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster. Chem Biol 10(12):1225-32.
5. He J, Hertweck C. (2004) Biosynthetic origin of the rare nitroaryl moiety of the polyketide antibiotic aureothin: involvement of an unprecedented N-oxygenase. J Am Chem Soc 126(12):3694-5. doi: 10.1021/ja039328t.
6. He J et al. (2004) Formation of the aureothin tetrahydrofuran ring by a bifunctional cytochrome p450 monooxygenase. J Am Chem Soc 126(51):16742-3. doi: 10.1021/ja046104h.
7. Ziehl M et al. (2005) Mutasynthesis of aureonitrile: an aureothin derivative with significantly improved cytostatic effect. Angew Chem Int Ed Engl 44(8):1202-5. doi: 10.1002/anie.200461990.
8. He J, Hertweck C. (2005) Functional analysis of the aureothin iterative type I polyketide synthase. Chembiochem 6(5):908-12. doi: 10.1002/cbic.200400333.
9. Muller M et al. (2006) Dissection of the late steps in aureothin biosynthesis. Chembiochem 7(1):37-9. doi: 10.1002/cbic.200500161.
10. Krebs C et al. (2007) AurF from Streptomyces thioluteus and a possible new family of manganese/iron oxygenases. Biochemistry 46(37):10413-8. doi: 10.1021/bi701060g. Epub 2007 Aug
11. Traitcheva N et al. (2007) Non-colinear polyketide biosynthesis in the aureothin and neoaureothin pathways: an evolutionary perspective. Chembiochem 8(15):1841-9. doi: 10.1002/cbic.200700309.
12. Zocher G et al. (2007) Structure and action of the N-oxygenase AurF from Streptomyces thioluteus. J Mol Biol 373(1):65-74. doi: 10.1016/j.jmb.2007.06.014. Epub 2007
13. Choi YS et al. (2008) In vitro reconstitution and crystal structure of p-aminobenzoate N-oxygenase (AurF) involved in aureothin biosynthesis. Proc Natl Acad Sci U S A 105(19):6858-63. doi:
14. Li N et al. (2010) Four-electron oxidation of p-hydroxylaminobenzoate to p-nitrobenzoate by a peroxodiferric complex in AurF from Streptomyces thioluteus. Proc Natl Acad Sci U S A 107(36):15722-7. doi:
15. Zocher G et al. (2011) Structural fine-tuning of a multifunctional cytochrome P450 monooxygenase. J Am Chem Soc 133(7):2292-302. doi: 10.1021/ja110146z. Epub 2011 Jan
16. Fries A et al. (2011) A ribonucleotide reductase-like electron transfer system in the nitroaryl-forming N-oxygenase AurF. Chembiochem 12(12):1832-5. doi: 10.1002/cbic.201100138. Epub 2011
17. Busch B et al. (2012) Interchenar retrotransfer of aureothin intermediates in an iterative polyketide synthase module. J Am Chem Soc 134(30):12382-5. doi: 10.1021/ja304454r. Epub 2012 Jul
18. Busch B et al. (2013) Multifactorial control of iteration events in a modular polyketide assembly line. Angew Chem Int Ed Engl 52(20):5285-9. doi: 10.1002/anie.201301322.
19. Sugimoto Y et al. (2014) Rational design of modular polyketide synthases: morphing the aureothin pathway into a luteoreticulin assembly line. Angew Chem Int Ed Engl 53(6):1560-4. doi: 10.1002/anie.201308176.
20. Chanco E et al. (2014) Characterization of the N-oxygenase AurF from Streptomyces thioletus. Bioorg Med Chem 22(20):5569-77. doi: 10.1016/j.bmc.2014.06.002. Epub
21. Werneburg M et al. (2010) Exploiting enzymatic promiscuity to engineer a focused library of highly selective antifungal and antiproliferative aureothin analogues. J Am Chem Soc 132(30):10407-13. doi: 10.1021/ja102751h.