8ODW

Crystal structure of LbmA Ox-ACP didomain in complex with NADP and ethyl glycinate from the lobatamide PKS (Gynuella sunshinyii)

Summary for 8ODW

• Entry DOI: 10.2210/pdb8odw/pdb
• Descriptor: Polyketide synthase modules-related protein, FLAVIN-ADENINE DINUCLEOTIDE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (8 entities in total)
• Functional Keywords: oxime, polyketide, oxidase, biosynthesis, biosynthetic protein
• Biological source: Gynuella sunshinyii
• Total number of polymer chains: 2
• Total formula weight: 147607.01

Authors

Francois, R.M.M.,Fraley, A.E.,Piel, J.,Weissman, K.J.,Gruez, A. (deposition date: 2023-03-09, release date: 2023-05-31, Last modification date: 2023-08-30)

Primary citation

Minas, H.A.,Francois, R.M.M.,Hemmerling, F.,Fraley, A.E.,Dieterich, C.L.,Rudisser, S.H.,Meoded, R.A.,Collin, S.,Weissman, K.J.,Gruez, A.,Piel, J.
Modular Oxime Formation by a trans-AT Polyketide Synthase.
Angew.Chem.Int.Ed.Engl., 62:e202304481-e202304481, 2023

PubMed Abstract: Modular trans-acyltransferase polyketide synthases (trans-AT PKSs) are enzymatic assembly lines that biosynthesize complex polyketide natural products. Relative to their better studied cis-AT counterparts, the trans-AT PKSs introduce remarkable chemical diversity into their polyketide products. A notable example is the lobatamide A PKS, which incorporates a methylated oxime. Here we demonstrate biochemically that this functionality is installed on-line by an unusual oxygenase-containing bimodule. Furthermore, analysis of the oxygenase crystal structure coupled with site-directed mutagenesis allows us to propose a model for catalysis, as well as identifying key protein-protein interactions that support this chemistry. Overall, our work adds oxime-forming machinery to the biomolecular toolbox available for trans-AT PKS engineering, opening the way to introducing such masked aldehyde functionalities into diverse polyketides.

PubMed: 37216334
DOI: 10.1002/anie.202304481

Experimental method

X-RAY DIFFRACTION (3.07 Å)