8GY0

Agrocybe pediades linalool sunthase (Ap.LS)

8GY0 の概要

• エントリーDOI: 10.2210/pdb8gy0/pdb
• 分子名称: Terpene synthase (2 entities in total)
• 機能のキーワード: monoterpene synthase, biosynthetic protein
• 由来する生物種: Agrocybe pediades
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74878.40

構造登録者

Rehka, T.,Sharma, D.,Lin, F.,Lim, C.,Choong, Y.K.,Chacko, J.,Zhang, C. (登録日: 2022-09-21, 公開日: 2023-04-12, 最終更新日: 2024-05-08)

主引用文献

T, R.,Sharma, D.,Lin, F.,Choong, Y.K.,Lim, C.,Jobichen, C.,Zhang, C.
Structural Understanding of Fungal Terpene Synthases for the Formation of Linear or Cyclic Terpene Products.
Acs Catalysis, 13:4949-4959, 2023

PubMed Abstract: Terpene synthases (TPSs), known gatekeepers of terpenoid diversity, are the main targets for enzyme engineering attempts. To this end, we have determined the crystal structure of linalool synthase (Ap.LS), which has been recently reported to be 44-fold and 287-fold more efficient than bacterial and plant counterparts, respectively. Structure-based molecular modeling followed by as well as tests confirmed that the region of 60-69aa and Tyr299 (adjacent to the motif "WxxxxxRY") are essential for maintaining Ap.LS specificity toward a short-chain (C10) acyclic product. Ap.LS Y299 mutants (Y299A, Y299C, Y299G, Y299Q, and Y299S) yielded long-chain (C15) linear or cyclic products. Molecular modeling based on the Ap.LS crystal structure indicated that farnesyl pyrophosphate in the binding pocket of Ap.LS Y299A has less torsion strain energy compared to the wild-type Ap.LS, which can be partially attributed to the larger space in Ap.LS Y299A for better accommodation of the longer chain (C15). Linalool/nerolidol synthase Y298 and humulene synthase Y302 mutations also produced C15 cyclic products similar to Ap.LS Y299 mutants. Beyond the three enzymes, our analysis confirmed that most microbial TPSs have asparagine at the position and produce mainly cyclized products (δ-cadinene, 1,8-cineole, epi-cubebol, germacrene D, β-barbatene, etc.). In contrast, those producing linear products (linalool and nerolidol) typically have a bulky tyrosine. The structural and functional analysis of an exceptionally selective linalool synthase, Ap.LS, presented in this work provides insights into factors that govern chain length (C10 or C15), water incorporation, and cyclization (cyclic vs acyclic) of terpenoid biosynthesis.

PubMed: 37066048
DOI: 10.1021/acscatal.2c05598

実験手法

X-RAY DIFFRACTION (1.988 Å)