Structural features of a new class of terpenoid cyclases.

ABA3 proteins are a group of terpenoid cyclases (TCs), which share very low sequence identity with known proteins and lack signature Mg²⁺ ion-binding motifs used to define TCs. The first characterised ABA3 from Botrytis cinerea catalyses the cyclisation of farnesyl pyrophosphate (FPP) via an unconventional process to produce (2Z,4E)-α-ionylideneethane, the skeleton of one of the major phytohormones-abscisic acid. We recently resolved the crystal structures of BcABA3 and two closely related proteins. BcABA3 and RuABA3 from fungi are (2Z,4E)-α-ionylideneethane synthases, whereas SkABA3 from a bacterium transforms FPP to sesquiterpene, whose identity remains unelucidated. ABA3 proteins adopt an all-α-helix fold that contains a Zn²⁺ ion-binding motif, and exploit unique features to coordinate Mg²⁺ ions and bind pyrophosphate of the substrate. In addition, the lid region undergoes extensive conformational change upon the binding of the substrate, and thoroughly covers the catalytic centre. The identification of ABA3 proteins is an important advance for natural product research, organic chemistry and enzymology, and the structural information summarised here should be important to guide in-depth investigations of this class of TCs.