6LZH

Crystal structure of Alpha/beta hydrolase GrgF from Penicillium sp. sh18

Summary for 6LZH

• Entry DOI: 10.2210/pdb6lzh/pdb
• Descriptor: GrgF, SODIUM ION (3 entities in total)
• Functional Keywords: catalysis, claisen condensation, hydrolase
• Biological source: Penicillium sp. sh18
• Total number of polymer chains: 2
• Total formula weight: 65808.95

Authors

Wang, H.,Yu, J.,Wang, W.G.,Matsuda, Y.,Yao, M. (deposition date: 2020-02-19, release date: 2020-06-24, Last modification date: 2023-11-29)

Primary citation

Wang, W.G.,Wang, H.,Du, L.Q.,Li, M.,Chen, L.,Yu, J.,Cheng, G.G.,Zhan, M.T.,Hu, Q.F.,Zhang, L.,Yao, M.,Matsuda, Y.
Molecular Basis for the Biosynthesis of an Unusual Chain-Fused Polyketide, Gregatin A.
J.Am.Chem.Soc., 142:8464-8472, 2020

PubMed Abstract: Gregatin A () is a fungal polyketide featuring an alkylated furanone core, but the biosynthetic mechanism to furnish the intriguing molecular skeleton has yet to be elucidated. Herein, we have identified the biosynthetic gene cluster of gregatin A () in sp. sh18 and investigated the mechanism that produces the intriguing structure of by in vivo and in vitro reconstitution of its biosynthesis. Our study established the biosynthetic route leading to and illuminated that is generated by the fusion of two different polyketide chains, which are, amazingly, synthesized by a single polyketide synthase GrgA with the aid of a -acting enoylreductase GrgB. Chain fusion, as well as chain hydrolysis, is catalyzed by an α/β hydrolase, GrgF, hybridizing the C and C carbon chains by Claisen condensation. Finally, structural analysis and mutational experiments using GrgF provided insight into how the enzyme facilitates the unusual chain-fusing reaction. In unraveling a new biosynthetic strategy involving a bifunctional PKS and a polyketide fusing enzyme, our study expands our knowledge concerning fungal polyketide biosynthesis.

PubMed: 32275405
DOI: 10.1021/jacs.0c02337

Experimental method

X-RAY DIFFRACTION (1.9 Å)