Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000122.1:
Cluster 1Polyketide136839

BGC0000122, phenylnannolone A biosynthetic gene cluster from Nannocystis pusilla. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: phenylnannolone A
ChemSpider ID: 27024549
SMILES string: Copy to clipboard
Molecular formula:
Average molecular mass: Da
Molecular activity: Inhibitor
Molecular target: inhibits the ABCB1 gene product P-glycoprotein (P-gp), thereby reversing daunorubicin resistance in cancer cells

Class-specific details

Biosynthetic class(es):
Polyketide
Polyketide subclass:
Aryl polyene (linear)
Polyketide synthase subclass:
Modular type I
Starter unit:
Other
Thioesterase type:
Unknown
Release / cyclization type:
Other

Modular polyketide synthases:
phn2 (AHN85651)
Module 0
AT specificity: Other
Evidence for specificity: Activity assay
Module 1
AT specificity: Ethylmalonyl-CoA
Evidence for specificity: Sequence-based prediction
KR stereochemistry: B-group
Module 2
AT specificity: Malonyl-CoA
Evidence for specificity: Sequence-based prediction
KR stereochemistry: B-group
Module 3
AT specificity: Malonyl-CoA
Evidence for specificity: Sequence-based prediction
Module 4
AT specificity: Malonyl-CoA
Evidence for specificity: Sequence-based prediction
KR stereochemistry: A-group

Gene cluster description

phenylnannolone A (BGC0000122). Gene Cluster 1. Biosynthetic class = Polyketide. GenBank KF739396. 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?incomplete
Evidence for cluster-compound connection:Enzymatic assays, Sequence-based prediction
MIxS-compliance:Unknown
Comments:cinnamic acid is adenylated by the AMP-ligase domain in the loading module to yield phenylnannolone A. The activity assay also showed reduced activation of p-coumaric acid which yields phenylnannolone C. first BCC/PKS system in microbial biosynthesis phn1 most likely involved in ethylmalonyl-CoA biosynthesis AT1 predominantly accepts ethylmalonyl-CoA to give rise to phenylnannolone A. However, phenylnannolone B, which contains a methyl instead of an ethyl branch, was also isolated. this indicates that AT1 can also accept methylmalonyl-CoA. Phenylnannolone A, however, is the dominant metabolite thus suggesting a preference for ethylmalonyl-CoA (which is in agreement with the bioinformatic analysis) The TE releases the polyketide under pyrone ring formation which is uncommon for modular typ I PKS systems
Contact for this cluster:Eric J.N. Helfrich (Institute of Microbiology ETH Zurich)

Literature references

1. Bouhired SM et al. (2014) Biosynthesis of phenylnannolone A, a multidrug resistance reversal agent from the halotolerant myxobacterium Nannocystis pusilla B150. Chembiochem 15(5):757-65. doi: 10.1002/cbic.201300676.
2. Ohlendorf B et al. (2008) Phenylnannolones A-C: biosynthesis of new secondary metabolites from the myxobacterium Nannocystis exedens. Chembiochem 9(18):2997-3003. doi: 10.1002/cbic.200800434.