Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000446.1:
Cluster 1NRP125846

BGC0000446, tilivalline biosynthetic gene cluster from Klebsiella oxytoca. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: tilivalline
PubChem ID: 128363
SMILES string: Copy to clipboard
Molecular formula: C20H19N3O2
Average molecular mass: 333.391 Da
Molecular activity: Cytotoxic

Class-specific details

Biosynthetic class(es):
NRP
Pyrrolobenzodiazepine (cyclic)
Thioesterase type:
None
Release / cyclization type:
Reductive release

Nonribosomal peptide synthetases:
npsA (CDG76957.1)
Module 0
A specificity: 2,3-Dihydroxybenzoic acid
Evidence for specificity: Feeding study
C domain subtype: N/A
npsB (CDG76959.1)
Module 1
A specificity: Proline
Evidence for specificity: Feeding study
C domain subtype: LCL

Gene cluster description

tilivalline (BGC0000446). Gene Cluster 1. Biosynthetic class = NRP. GenBank Not derived from GenBank. 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:Gene expression correlated with compound production
MIxS-compliance:Unknown
Contact for this cluster:Hendrik Wolff (AK Bode, Goethe University, Germany)

Literature references

1. Schneditz G et al. (2014) Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis. Proc Natl Acad Sci U S A 111(36):13181-6. doi:
2. Dornisch E et al. (2017) Biosynthesis of the Enterotoxic Pyrrolobenzodiazepine Natural Product Tilivalline. Angew Chem Int Ed Engl 56(46):14753-14757. doi:
3. Tse H et al. (2017) A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis. J Biol Chem 292(47):19503-19520. doi: 10.1074/jbc.M117.791558. Epub
4. von Tesmar A et al. (2018) Biosynthesis of the Klebsiella oxytoca Pathogenicity Factor Tilivalline: Heterologous Expression, in Vitro Biosynthesis, and Inhibitor Development. ACS Chem Biol 13(3):812-819. doi: 10.1021/acschembio.7b00990. Epub