Li Siyu, Huang Jian-Wen, Min Jian, Li Hao, Ning Meidan, Zhou Shuyu, Yang Yu, Chen Chun-Chi, Guo Rey-Ting
State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei University, Wuhan, China.
Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China.
Nat Commun. 2025 Jan 2;16(1):207. doi: 10.1038/s41467-024-55717-6.
Terpenoid cyclases (TCs) account for the synthesis of the most widespread and diverse natural compounds. A sesquiterpene cyclase termed BcABA3 from an abscisic acid-producing fungus Botrytis cinerea that yields (2Z,4E)-α-ionylideneethane but lacks signature feature of canonical TCs represents a distinct type of TCs. Here, we report the crystal structures of BcABA3, a closely related RuABA3 from Rutstroemia sp. and a bacterial SkABA3 from Shimazuella kribbensis. These ABA3 proteins adopt an all-α-helix fold and bind pyrophosphate moiety of farnesyl pyrophosphate by Glu-chelated Mg ion cluster. We conduct mutagenesis experiments to validate the role of the substrate-binding residues. SkABA3 appears to yield compounds that are distinct from (2Z,4E)-α-ionylideneethane. These results not only provide the molecular insight into ABA3 proteins that serve as an important basis to the future investigation of this class of TCs, but also reveal the existence of more uncharacterized terpenoids synthesized via dedicated machineries.
萜类环化酶（TCs）负责合成最为广泛多样的天然化合物。一种来自产脱落酸的真菌灰葡萄孢的倍半萜环化酶，名为BcABA3，它能产生（2Z,4E）-α-紫罗烯亚基乙烷，但缺乏典型TCs的标志性特征，代表了一种独特类型的TCs。在此，我们报道了BcABA3、来自Rutstroemia sp.的密切相关的RuABA3以及来自Shimazuella kribbensis的细菌SkABA3的晶体结构。这些ABA3蛋白采用全α螺旋折叠结构，并通过Glu螯合的Mg离子簇结合法尼基焦磷酸的焦磷酸部分。我们进行了诱变实验以验证底物结合残基的作用。SkABA3似乎产生与（2Z,4E）-α-紫罗烯亚基乙烷不同的化合物。这些结果不仅为ABA3蛋白提供了分子层面的见解，这是未来对这类TCs进行研究的重要基础，还揭示了通过专门机制合成的更多未被表征的萜类化合物的存在。
