9MC1

Trans-acting enoylreductase PhiaB involved in the phialotideA biosynthesis pathway

Summary for 9MC1

• Entry DOI: 10.2210/pdb9mc1/pdb
• Descriptor: Trans-acting enoylreductase (2 entities in total)
• Functional Keywords: trans-acting enoylreductases, oxidoreductase
• Biological source: Pseudophialophora
• Total number of polymer chains: 1
• Total formula weight: 40083.37

Authors

Takekawa, Y.,Takino, J.,Sato, S.,Yabuno, N.,Oikawa, H.,Ose, T.,Minami, A. (deposition date: 2025-03-17, release date: 2025-04-16)

Primary citation

Takekawa, Y.,Takino, J.,Sato, S.,Oikawa, H.,Ose, T.,Minami, A.
Chain-length preference of trans-acting enoylreductases involved in the biosynthesis of fungal polyhydroxy polyketides.
Biochem.Biophys.Res.Commun., 761:151737-151737, 2025

PubMed Abstract: Fungal polyketides are diverse natural products synthesized by iterative polyketide synthases (i-PKSs) and modified by enzymes such as trans-acting enoylreductases (trans-ERs). In this study, we investigated PhiaB and PhomB, trans-ERs involved in the biosynthesis of polyhydroxy polyketides, phialotides, and phomenoic acids. In vitro assays using substrate analogs revealed distinct chain-length preferences. X-ray structural analysis of PhiaB revealed distinct N-terminal, central, and C-terminal regions. The importance of the central region, which possesses a canonical Rossmann fold for cofactor recognition, was further supported by biosynthetic refactoring using a chimeric enzyme. Docking studies revealed key amino acid residues that may be involved in substrate/cofactor recognition. These findings advance our understanding of trans-ER function, providing opportunities for the synthesis of structurally different polyhydroxy polyketides by genetic engineering of polyhydroxy polyketide biosynthesis.

PubMed: 40186921
DOI: 10.1016/j.bbrc.2025.151737

Experimental method

X-RAY DIFFRACTION (2.9 Å)