8CJH

Architecture of a PKS-NRPS hybrid megaenzyme involved in the biosynthesis of the genotoxin colibactin

Summary for 8CJH

• Entry DOI: 10.2210/pdb8cjh/pdb
• Descriptor: Colibactin hybrid non-ribosomal peptide synthetase/type I polyketide synthase ClbK (1 entity in total)
• Functional Keywords: polyketide synthase, ketosynthase domain, acyltransferase domain, acyl carrier protein domain, biosynthetic protein
• Biological source: Escherichia coli
• Total number of polymer chains: 6
• Total formula weight: 512582.39

Authors

Bonhomme, S.,Dessen, A.,Macheboeuf, P. (deposition date: 2023-02-13, release date: 2023-04-26, Last modification date: 2024-06-19)

Primary citation

Bonhomme, S.,Contreras-Martel, C.,Dessen, A.,Macheboeuf, P.
Architecture of a PKS-NRPS hybrid megaenzyme involved in the biosynthesis of the genotoxin colibactin.
Structure, 31:700-, 2023

PubMed Abstract: The genotoxin colibactin produced by Escherichia coli is involved in the development of colorectal cancers. This secondary metabolite is synthesized by a multi-protein machinery, mainly composed of non-ribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) enzymes. In order to decipher the function of a PKS-NRPS hybrid enzyme implicated in a key step of colibactin biosynthesis, we conducted an extensive structural characterization of the ClbK megaenzyme. Here we present the crystal structure of the complete trans-AT PKS module of ClbK showing structural specificities of hybrid enzymes. In addition, we report the SAXS solution structure of the full-length ClbK hybrid that reveals a dimeric organization as well as several catalytic chambers. These results provide a structural framework for the transfer of a colibactin precursor through a PKS-NRPS hybrid enzyme and can pave the way for re-engineering PKS-NRPS hybrid megaenzymes to generate diverse metabolites with many applications.

PubMed: 37059096
DOI: 10.1016/j.str.2023.03.012

Experimental method

X-RAY DIFFRACTION (2.982 Å)