7PHD

Chimeric carminomycin-4-O-methyltransferase (DnrK) with a region from 10-decarboxylase TamK

7PHD の概要

• エントリーDOI: 10.2210/pdb7phd/pdb
• 関連するPDBエントリー: 1TW2
• 分子名称: Carminomycin 4-O-methyltransferase DnrK,Methyltransferase domain-containing protein, SULFATE ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: carminomycin-4-o-methyltransferase variant; chimeragenesis; tsukubarubicin 10-decarboxylase; biosynthetic protein, biosynthetic protein
• 由来する生物種: Streptomyces peucetius; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 82885.77

構造登録者

Grocholski, T.,Dinis, P.,MetsaKetela, M. (登録日: 2021-08-17, 公開日: 2022-09-07, 最終更新日: 2024-02-07)

主引用文献

Dinis, P.,Tirkkonen, H.,Wandi, B.N.,Siitonen, V.,Niemi, J.,Grocholski, T.,Metsa-Ketela, M.
Evolution-inspired engineering of anthracycline methyltransferases.
Pnas Nexus, 2:pgad009-pgad009, 2023

PubMed Abstract: soil bacteria produce hundreds of anthracycline anticancer agents with a relatively conserved set of genes. This diversity depends on the rapid evolution of biosynthetic enzymes to acquire novel functionalities. Previous work has identified -adenosyl-l-methionine-dependent methyltransferase-like proteins that catalyze 4-O-methylation, 10-decarboxylation, or 10-hydroxylation, with additional differences in substrate specificities. Here we focused on four protein regions to generate chimeric enzymes using sequences from four distinct subfamilies to elucidate their influence in catalysis. Combined with structural studies we managed to depict factors that influence gain-of-hydroxylation, loss-of-methylation, and substrate selection. The engineering expanded the catalytic repertoire to include novel 9,10-elimination activity, and 4-O-methylation and 10-decarboxylation of unnatural substrates. The work provides an instructive account on how the rise of diversity of microbial natural products may occur through subtle changes in biosynthetic enzymes.

PubMed: 36874276
DOI: 10.1093/pnasnexus/pgad009

実験手法

X-RAY DIFFRACTION (1.53 Å)