8QD1

Ayg1p from A. fumigatus catalyzes polyketide shortening in the biosynthesis of DHN-melanin

8QD1 の概要

• エントリーDOI: 10.2210/pdb8qd1/pdb
• 関連するPDBエントリー: 6HXA
• 分子名称: Pigment biosynthesis protein yellowish-green 1 (2 entities in total)
• 機能のキーワード: natural product biosynthesis, polyketide synthase system, alpha, beta-hydrolase fold, polyketide shortening, retro claisen reaction, lyase
• 由来する生物種: Aspergillus fumigatus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 189761.64

構造登録者

Schmalhofer, M.,Vagstad, A.L.,Zhou, Q.,Bode, H.B.,Groll, M. (登録日: 2023-08-28, 公開日: 2024-03-13, 最終更新日: 2024-06-19)

主引用文献

Schmalhofer, M.,Vagstad, A.L.,Zhou, Q.,Bode, H.B.,Groll, M.
Polyketide Trimming Shapes Dihydroxynaphthalene-Melanin and Anthraquinone Pigments.
Adv Sci, 11:e2400184-e2400184, 2024

PubMed Abstract: Pigments such as anthraquinones (AQs) and melanins are antioxidants, protectants, or virulence factors. AQs from the entomopathogenic bacterium Photorhabdus laumondii are produced by a modular type II polyketide synthase system. A key enzyme involved in AQ biosynthesis is PlAntI, which catalyzes the hydrolysis of the bicyclic-intermediate-loaded acyl carrier protein, polyketide trimming, and assembly of the aromatic AQ scaffold. Here, multiple crystal structures of PlAntI in various conformations and with bound substrate surrogates or inhibitors are reported. Structure-based mutagenesis and activity assays provide experimental insights into the three sequential reaction steps to yield the natural product AQ-256. For comparison, a series of ligand-complex structures of two functionally related hydrolases involved in the biosynthesis of 1,8-dihydroxynaphthalene-melanin in pathogenic fungi is determined. These data provide fundamental insights into the mechanism of polyketide trimming that shapes pigments in pro- and eukaryotes.

PubMed: 38491909
DOI: 10.1002/advs.202400184

実験手法

X-RAY DIFFRACTION (1.7 Å)