7R0X

Structure of the branching thioesterase from oocydin biosynthesis

Summary for 7R0X

• Entry DOI: 10.2210/pdb7r0x/pdb
• Descriptor: Polyketide synthase (2 entities in total)
• Functional Keywords: thioesterase, polyketide, acylation, hydrolase
• Biological source: Serratia
• Total number of polymer chains: 1
• Total formula weight: 41102.43

Authors

Fraley, A.E.,Piel, J. (deposition date: 2022-02-02, release date: 2022-08-10, Last modification date: 2024-11-06)

Primary citation

Fraley, A.E.,Dieterich, C.L.,Mabesoone, M.F.J.,Minas, H.A.,Meoded, R.A.,Hemmerling, F.,Piel, J.
Structure of a Promiscuous Thioesterase Domain Responsible for Branching Acylation in Polyketide Biosynthesis.
Angew.Chem.Int.Ed.Engl., 61:e202206385-e202206385, 2022

PubMed Abstract: Thioesterases (TEs) are fundamentally important enzymes present in all bacteria and eukaryotes, where they have conserved functions in fatty acid biosynthesis and secondary metabolism. This work provides the first structural insights into a functionally distinct group of TEs that perform diverse acylations in polyketide and peptide biosynthesis (TE s). Structural analysis of the oocydin (OocS) TE domain facilitated identification and engineering of the active site to modulate acyl-group acceptance. In this way, we achieved higher reactivity using a structure-based approach, building a foundation for biocatalytic development of TE -mediated O-acylation, a modification known to improve the bioactivity of oocydin-type polyketides. Lastly, the promiscuity of the OocS TE motivated us to investigate, and ultimately provide evidence for, the production of longer chain branched oocydins in the native host Serratia plymuthica 4Rx13. This work frames the OocS TE and homologs as invaluable synthetic biology tools for polyketide drug development.

PubMed: 35903999
DOI: 10.1002/anie.202206385

Experimental method

X-RAY DIFFRACTION (2.83 Å)