Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000355.1:
Cluster 1NRP124812

BGC0000355, fumiquinazolines biosynthetic gene cluster from Aspergillus fumigatus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: fumiquinazoline A
PubChem ID: 11247802
SMILES string: Copy to clipboard
Molecular formula: C24H23N5O4
Average molecular mass: 445.479 Da
Molecular activity: Cytotoxic

Class-specific details

Biosynthetic class(es):
NRP
Other (cyclic)
Thioesterase type:
Unknown
Release / cyclization type:
Other

Nonribosomal peptide synthetases:
XP_751087.1
Module 1
A specificity: Anthranilate
Evidence for specificity: Activity assay
C domain subtype: LCL
Module 2
A specificity: Tryptophan
Evidence for specificity: Activity assay
AA is epimerized
C domain subtype: LCL
Module 3
A specificity: Alanine
Evidence for specificity: Structure-based inference
C domain subtype: Heterocyclization
XP_751084.1
Module 1
A specificity: Alanine
Evidence for specificity: Activity assay
C domain subtype: Heterocyclization

Gene cluster description

fumiquinazolines (BGC0000355). Gene Cluster 1. Biosynthetic class = NRP. GenBank CM000174, positions 3009975-3035305. 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
Contact for this cluster:Philipp Wiemann, Nancy Keller (University of Wisconsin-Madison)

Literature references

1. Ames BD et al. (2011) Complexity generation in fungal peptidyl alkaloid biosynthesis: oxidation of fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the flavoenzyme Af12070 from Aspergillus fumigatus. Biochemistry 50(40):8756-69. doi: 10.1021/bi201302w. Epub 2011 Sep
2. Ames BD, Walsh CT. (2010) Anthranilate-activating modules from fungal nonribosomal peptide assembly lines. Biochemistry 49(15):3351-65. doi: 10.1021/bi100198y.
3. Ames BD et al. (2010) Enzymatic processing of fumiquinazoline F: a tandem oxidative-acylation strategy for the generation of multicyclic scaffolds in fungal indole alkaloid biosynthesis. Biochemistry 49(39):8564-76. doi: 10.1021/bi1012029. Epub 2010 Sep 8.
4. O'Hanlon KA et al. (2012) Nonribosomal peptide synthetase genes pesL and pes1 are essential for Fumigaclavine C production in Aspergillus fumigatus. Appl Environ Microbiol 78(9):3166-76. doi: 10.1128/AEM.07249-11. Epub
5. Gao X et al. (2012) Cyclization of fungal nonribosomal peptides by a terminal condensation-like domain. Nat Chem Biol 8(10):823-30. doi: 10.1038/nchembio.1047.
6. Haynes SW et al. (2013) Complexity generation in fungal peptidyl alkaloid biosynthesis: a two-enzyme pathway to the hexacyclic MDR export pump inhibitor ardeemin. ACS Chem Biol 8(4):741-8. doi: 10.1021/cb3006787. Epub 2013 Feb 6.
7. Tsunematsu Y et al. (2013) Distinct mechanisms for spiro-carbon formation reveal biosynthetic pathway crosstalk. Nat Chem Biol 9(12):818-25. doi: 10.1038/nchembio.1366. Epub 2013 Oct