Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000356.1:
Cluster 1NRP / Alkaloid127708

BGC0000356, fumitremorgin biosynthetic gene cluster from Aspergillus fumigatus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: verruculogen
PubChem ID: 104862
SMILES string: Copy to clipboard
Molecular formula: C27H33N3O7
Average molecular mass: 511.575 Da
Molecular activity: Inhibitor
Molecular target: M phase inhibitor of cell cycle

Class-specific details

Biosynthetic class(es):
NRP / Alkaloid
Other (linear)
Thioesterase type:
None
Release / cyclization type:
Hydrolysis

Nonribosomal peptide synthetases:
ftmA/ftmPS (BAH23995.1)
Module 1
A specificity: Tryptophan / Proline
Evidence for specificity: Structure-based inference
C domain subtype: LCL
Module 2
A specificity: Proline / Tryptophan
Evidence for specificity: Structure-based inference
C domain subtype: LCL
Alkaloid subclass:
Indole/benzopyrrole

Gene cluster description

fumitremorgin (BGC0000356). Gene Cluster 1. Biosynthetic class = NRP/Alkaloid. GenBank AB436628, positions 321-22997. 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
MIxS-compliance:Unknown
Comments:ftmI/ftmO do not catalyze any enzymatic reactions, this has been shown by knock-out studies, and are therefore not regarded as part of the cluster. A. fumigatus Af293 harbors a point mutation in ftmMT N. fischeri NRRL181 produces fumitremorgin A catalyzed by ftmPT3 present outside the genomic context of the cluster homologous to A. fumigatus
Contact for this cluster:Philipp Wiemann, Nancy Keller (University of Wisconsin-Madison)

Literature references

1. Cui CB et al. (1996) Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. II. Physico-chemical properties and structures. J Antibiot (Tokyo) 49(6):534-40.
2. Ahmed-Belkacem A et al. (2006) Inhibitors of cancer cell multidrug resistance mediated by breast cancer resistance protein (BCRP/ABCG2). Anticancer Drugs 17(3):239-43.
3. Usui T et al. (1998) Tryprostatin A, a specific and novel inhibitor of microtubule assembly. Biochem J 333 ( Pt 3):543-8.
4. Jain HD et al. (2008) Synthesis and structure-activity relationship studies on tryprostatin A, an inhibitor of breast cancer resistance protein. Bioorg Med Chem 16(8):4626-51. doi: 10.1016/j.bmc.2008.02.050. Epub
5. Liu H et al. (2006) Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Int J Oncol 29(5):1237-46.
6. Maiya S et al. (2006) The fumitremorgin gene cluster of Aspergillus fumigatus: identification of a gene encoding brevianamide F synthetase. Chembiochem 7(7):1062-9. doi: 10.1002/cbic.200600003.
7. Grundmann A et al. (2008) FtmPT2, an N-prenyltransferase from Aspergillus fumigatus, catalyses the last step in the biosynthesis of fumitremorgin B. Chembiochem 9(13):2059-63. doi: 10.1002/cbic.200800240.
8. Kato N et al. (2009) Identification of cytochrome P450s required for fumitremorgin biosynthesis in Aspergillus fumigatus. Chembiochem 10(5):920-8. doi: 10.1002/cbic.200800787.
9. Steffan N et al. (2009) FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus. Org Biomol Chem 7(19):4082-7. doi: 10.1039/b908392h. Epub 2009 Aug 6.
10. Mundt K et al. (2012) Identification of the verruculogen prenyltransferase FtmPT3 by a combination of chemical, bioinformatic and biochemical approaches. Chembiochem 13(17):2583-92. doi: 10.1002/cbic.201200523. Epub 2012
11. Kato N et al. (2013 TI) A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in Aspergillus fumigatus strain Af293. Biosci Biotechnol Biochem 77(5):1061-7. doi: 10.1271/bbb.130026. Epub 2013
12. Wiemann P et al. (2013) Prototype of an intertwined secondary-metabolite supercluster. Proc Natl Acad Sci U S A 110(42):17065-70. doi: