Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0001017.1:
Cluster 1NRP / Polyketide163626

BGC0001017, microcystin biosynthetic gene cluster from Microcystis aeruginosa. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: microcystin LR
PubChem ID: 445434
ChEBI ID: 6925
ChEMBL ID: 444092
ChemSpider ID: 4941647
SMILES string: Copy to clipboard
Molecular formula: C49H74N10O12
Average molecular mass: 995.189 Da
Molecular activity: Cytotoxic, Inhibitor
Molecular target: Eucaryotic protein phosphatases type 1 and 2A

Class-specific details

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

Nonribosomal peptide synthetases:
mcyG (AAF00957.1)
Module 0
A specificity: Phenylacetate
Evidence for specificity: Structure-based inference
C domain subtype: N/A
mcyE (AAF00958.1)
Module 3
A specificity: Glutamate
Evidence for specificity: Structure-based inference
C domain subtype: LCL
Module 4
A specificity: Unknown
Evidence for specificity: Unknown
C domain subtype: LCL
mcyA (AAF00960.1)
Module 6
A specificity: Serine
Evidence for specificity: Activity assay
C domain subtype: N/A
Scaffold-modifying domain: Methylation
Module 7
A specificity: Alanine
Evidence for specificity: Activity assay
AA is epimerized
C domain subtype: DCL
mcyB (AAF00961.1)
Module 8
A specificity: Leucine
Evidence for specificity: Activity assay
C domain subtype: DCL
Module 9
A specificity: D-N2-methylasparagine
Evidence for specificity: Activity assay
C domain subtype: LCL
mcyC (AAF00962.1)
Module 10
A specificity: Arginine
Evidence for specificity: Activity assay
C domain subtype: LCL
Polyketide subclass:
Other (cyclic)
Polyketide synthase subclass:
Modular type I
Starter unit:
Other
Thioesterase type:
None
Release / cyclization type:
Hydrolysis

Modular polyketide synthases:
mcyG (AAF00957.1)
Module 1
AT specificity: None
Evidence for specificity: Structure-based inference
KR stereochemistry: Unknown
Scaffold-modifying domain: Methylation

mcyE (AAF00958.1)
Module 2
AT specificity: Malonyl-CoA
Evidence for specificity: Structure-based inference
Scaffold-modifying domain: Methylation

mcyD (AAF00959.1)
Module 5
KR stereochemistry: Unknown
Scaffold-modifying domain: Methylation
Module 6
AT specificity: Malonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: Unknown
Scaffold-modifying domain: None

Gene cluster description

microcystin (BGC0001017). Gene Cluster 1. Biosynthetic class = NRP/Polyketide. GenBank AF183408. 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, Sequence-based prediction
MIxS-compliance:Unknown
Comments:This cyclic peptide is an inhibitors of eukaryotic protein phosphatases type 1 and 2A. Synthesized nonribosomally by RNPS, PKS and hybrid PKS-NRPPS enzymes, the microcystins contain a number of unusual amino acid residues including the L-amino polyketide moiety Adda (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid).
Contact for this cluster:Brett Neilan (School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia)

Literature references

1. Tillett D et al. (2000) Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: an integrated peptide-polyketide synthetase system. Chem Biol 7(10):753-64.
2. Sielaff H et al. (2003) The mcyF gene of the microcystin biosynthetic gene cluster from Microcystis aeruginosa encodes an aspartate racemase. Biochem J 373(Pt 3):909-16. doi: 10.1042/BJ20030396.
3. Pearson LA et al. (2004) Inactivation of an ABC transporter gene, mcyH, results in loss of microcystin production in the cyanobacterium Microcystis aeruginosa PCC 7806. Appl Environ Microbiol 70(11):6370-8. doi:
4. Pearson LA et al. (2007) Characterization of the 2-hydroxy-acid dehydrogenase McyI, encoded within the microcystin biosynthesis gene cluster of Microcystis aeruginosa PCC7806. J Biol Chem 282(7):4681-92. doi: 10.1074/jbc.M606986200. Epub 2006
5. Hicks LM et al. (2006) Structural characterization of in vitro and in vivo intermediates on the loading module of microcystin synthetase. ACS Chem Biol 1(2):93-102. doi: 10.1021/cb500007v.
6. Meyer S et al. (2016) Biochemical Dissection of the Natural Diversification of Microcystin Provides Lessons for Synthetic Biology of NRPS. Cell Chem Biol 23(4):462-71. doi: 10.1016/j.chembiol.2016.03.011.
7. Liu T et al. (2017) Directing the Heterologous Production of Specific Cyanobacterial Toxin Variants. ACS Chem Biol 12(8):2021-2029. doi: 10.1021/acschembio.7b00181. Epub