Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000967.1:
Cluster 1NRP / Polyketide1148229

BGC0000967, calyculin biosynthetic gene cluster from uncultured Candidatus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: calyculin A
PubChem ID: 5311365
SMILES string: Copy to clipboard
Molecular formula: C50H81N4O15P
Average molecular mass: 1009.185 Da
Molecular activity: Cytotoxic
Molecular target: inhibition of protein phosphatase 1 and 2A

Class-specific details

Biosynthetic class(es):
NRP / Polyketide
Other (linear)
Thioesterase type:
Type I
Release / cyclization type:
Unknown

Nonribosomal peptide synthetases:
calA (BAP05589.1)
Module 0
A specificity: Serine
Evidence for specificity: Sequence-based prediction
C domain subtype: N/A
Scaffold-modifying domain: Methylation
calB (BAP05590.1)
Module 4
A specificity: Glycine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Module 8
A specificity: Unknown
Evidence for specificity: Unknown
C domain subtype: LCL
Scaffold-modifying domain: Other
calC (BAP05591.1)
Module 8
A specificity: Serine
Evidence for specificity: Sequence-based prediction
C domain subtype: N/A
calH (BAP05596.1)
Module 29
A specificity: Alanine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
calI (BAP05597.1)
Module 33
A specificity: Serine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Polyketide subclass:
Other (linear)
Polyketide synthase subclass:
Trans-AT type I
Starter unit:
Other
BAP05573.1
Thioesterase type:
None
Release / cyclization type:
Unknown

Modular polyketide synthases:
calA (BAP05589.1)
Module 1
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Methylation
Module is non-elongating
Evidence for non-elongation: Unknown
Module 2
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Methylation

calB (BAP05590.1)
Module 3
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 5
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 6
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module 7
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None

calC (BAP05591.1)
Module 9
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Oxidation
Module is non-elongating
Evidence for non-elongation: Unknown
Module 10
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Oxidation
Module is non-elongating
Evidence for non-elongation: Unknown
Module 11
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Oxidation
Module is non-elongating
Evidence for non-elongation: Unknown

calE (BAP05593.1)
Module 12
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 13
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 14
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 15
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 16
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 17
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 18
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown

calF (BAP05594.1)
Module 19
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 20
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 21
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 22
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 23
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown

calG (BAP05595.1)
Module 23
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Methylation
Module 24
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Methylation
Module 25
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Methylation
Module 26
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Methylation
Module 27
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Methylation

calH (BAP05596.1)
Module 28
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Beta-branching
Module 30
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Beta-branching
Module 31
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: Beta-branching

calI (BAP05597.1)
Module 31
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown
Module 32
AT specificity: N/A
Evidence for specificity: Sequence-based prediction
Scaffold-modifying domain: None
Module is non-elongating
Evidence for non-elongation: Unknown

Gene cluster description

Download cluster GenBank file
calyculin (BGC0000967). Gene Cluster 1. Biosynthetic class = NRP/Polyketide. GenBank AB933566. 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
Contact for this cluster:Eric J. N. Helfrich (Institute of Microbiology, Eidgenossische Technische Hochschule (ETH) Zurich, Piel lab)

Literature references

1. Wakimoto T et al. (2014) Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont. Nat Chem Biol 10(8):648-55. doi: 10.1038/nchembio.1573. Epub 2014 Jun
2. Fagerholm AE et al. (2010) Calyculins and related marine natural products as serine-threonine protein phosphatase PP1 and PP2A inhibitors and total syntheses of calyculin A, B, and C. Mar Drugs 8(1):122-72. doi: 10.3390/md80100122.
3. Dumdei EJ et al. (1997) Isolation of Calyculins, Calyculinamides, and Swinholide H from the New Zealand Deep-Water Marine Sponge Lamellomorpha strongylata. J Org Chem 62(8):2636-2639.
4. Wakimoto T et al. (2002) Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A. Chem Biol 9(3):309-19.