4RO5

Crystal structure of the SAT domain from the non-reducing fungal polyketide synthase CazM

4RO5 の概要

• エントリーDOI: 10.2210/pdb4ro5/pdb
• 分子名称: SAT domain from CazM, GLYCEROL (3 entities in total)
• 機能のキーワード: non reducing polyketide synthase, acyl carrier protein transacylase, transferase
• 由来する生物種: Chaetomium globosum CBS 148.51 (Soil fungus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44760.27

構造登録者

Winter, J.M.,Cascio, D.,Sawaya, M.R.,Tang, Y. (登録日: 2014-10-27, 公開日: 2015-09-09, 最終更新日: 2017-11-22)

主引用文献

Winter, J.M.,Cascio, D.,Dietrich, D.,Sato, M.,Watanabe, K.,Sawaya, M.R.,Vederas, J.C.,Tang, Y.
Biochemical and Structural Basis for Controlling Chemical Modularity in Fungal Polyketide Biosynthesis.
J.Am.Chem.Soc., 137:9885-9893, 2015

PubMed Abstract: Modular collaboration between iterative fungal polyketide synthases (IPKSs) is an important mechanism for generating structural diversity of polyketide natural products. Inter-PKS communication and substrate channeling are controlled in large by the starter unit acyl carrier protein transacylase (SAT) domain found in the accepting IPKS module. Here, we reconstituted the modular biosynthesis of the benzaldehyde core of the chaetoviridin and chaetomugilin azaphilone natural products using the IPKSs CazF and CazM. Our studies revealed a critical role of CazM's SAT domain in selectively transferring a highly reduced triketide product from CazF. In contrast, a more oxidized triketide that is also produced by CazF and required in later stages of biosynthesis of the final product is not recognized by the SAT domain. The structural basis for the acyl unit selectivity was uncovered by the first X-ray structure of a fungal SAT domain, highlighted by a covalent hexanoyl thioester intermediate in the SAT active site. The crystal structure of SAT domain will enable protein engineering efforts aimed at mixing and matching different IPKS modules for the biosynthesis of new compounds.

PubMed: 26172141
DOI: 10.1021/jacs.5b04520

実験手法

X-RAY DIFFRACTION (1.6 Å)