Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0001110.1:
Cluster 1NRP / Polyketide172054

BGC0001110, psymberin biosynthetic gene cluster from uncultured bacterium. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: psymberin
PubChem ID: 11456257
SMILES string: Copy to clipboard
Molecular formula: C31H47NO11
Average molecular mass: 609.713 Da
Molecular activity: Cytotoxic
Molecular target: RPL41 (C. elegans), RPL36a and RPL36aI (human ortholog)

Class-specific details

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

Nonribosomal peptide synthetases:
ADA82585.1
Module 4
A specificity: Glycine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Polyketide subclass:
Other (linear)
Polyketide synthase subclass:
Trans-AT type I
Starter unit:
Acetyl-CoA
ADA82589.1
Thioesterase type:
Unknown
Release / cyclization type:
Unknown

Modular polyketide synthases:
ADA82581.1
Module 0
AT specificity: Acetyl-CoA
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module 1
Scaffold-modifying domain: Other
Module 2
KR stereochemistry: Unknown
Scaffold-modifying domain: Other

ADA82585.1
Module 10
Scaffold-modifying domain: Methylation
Module 11
Scaffold-modifying domain: None
Module 12
Scaffold-modifying domain: Other
Module 3
Scaffold-modifying domain: Methylation
Module is non-elongating
Evidence for non-elongation: Unknown
Module 5
KR stereochemistry: Unknown
Scaffold-modifying domain: None
Module 6
KR stereochemistry: Unknown
Scaffold-modifying domain: Methylation
Module 7
KR stereochemistry: Unknown
Scaffold-modifying domain: Pyran synthase
Module 8
KR stereochemistry: Unknown
Scaffold-modifying domain: Methylation
Module 9
KR stereochemistry: Unknown
Scaffold-modifying domain: None

Gene cluster description

psymberin (BGC0001110). Gene Cluster 1. Biosynthetic class = NRP/Polyketide. GenBank FJ823461, positions 1-72054. 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:Enzymatic assays, Sequence-based prediction
MIxS-compliance:Unknown
Comments:Psymberin harbors an isocoumarin group, hence it is cyclized and contains a lactone. However, it is not a macrolactone.
Contact for this cluster:Eric J. N. Helfrich (Institute of Microbiology, ETH Zurich, Piel lab)

Literature references

1. Fisch KM et al. (2009) Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting. Nat Chem Biol 5(7):494-501. doi: 10.1038/nchembio.176.
2. Cichewicz RH et al. (2004) Psymberin, a potent sponge-derived cytotoxin from Psammocinia distantly related to the pederin family. Org Lett 6(12):1951-4. doi: 10.1021/ol049503q.
3. Wu CY et al. (2012) Studies toward the unique pederin family member psymberin: structure-activity relationships, biochemical studies, and genetics identify the mode-of-action of psymberin. J Am Chem Soc 134(46):18998-9003. doi: 10.1021/ja3057002. Epub 2012
4. Bielitza M, Pietruszka J. (2013) The psymberin story--biological properties and approaches towards total and analogue syntheses. Angew Chem Int Ed Engl 52(42):10960-85. doi: 10.1002/anie.201301259.
5. Jenner M et al. (2015) Acyl-chain elongation drives ketosynthase substrate selectivity in trans-acyltransferase polyketide synthases. Angew Chem Int Ed Engl 54(6):1817-21. doi: 10.1002/anie.201410219.
6. Jenner M et al. (2013) Substrate specificity in ketosynthase domains from trans-AT polyketide synthases. Angew Chem Int Ed Engl 52(4):1143-7. doi: 10.1002/anie.201207690.
7. Pettit GR et al. (2004) Antineoplastic agents. 520. Isolation and structure of irciniastatins A and B from the Indo-Pacific marine sponge Ircinia ramosa. J Med Chem 47(5):1149-52. doi: 10.1021/jm030207d.