A monodomain class II terpene cyclase assembles complex isoprenoid scaffolds
Steroids and hopanoids have important functions in diverse organisms. They are generated by multidomain class II terpene cyclases via complex cascade reactions. A recent “Nature Chemistry” paper by the Piel (IMB) and Groll groups (TU Munich) reporting structures of a monodomain cyclase sheds light on the function and evolution of such enzymes.
In the known modern type II cyclases, two domains termed β and γ together form a reaction chamber that orients the substrate for correct polycyclization. These have likely formed by fusion of unknown single-domain proteins. The monodomain cyanobacterial merosterolic acid synthase (MstE) presented in the publication lacks a membrane-bound γ-domain but is still capable of producing a polycyclic, steroid-like product. High-resolution crystal structures of MstE with bound substrate and product provide detailed insights into the catalytic cascade. While the reactive center is found in the β-domain, the γ-domain is replaced by a set of expanded, unstructured loops. These provide residues stabilizing reactive cyclization intermediates. The data suggest that ancient, minimalistic cyclases might have already been capable of producing complex terpene biomolecules. Due to the solubility of the MstE, biotechnological applications can be envisaged that are explored in the paper.
Link to the paper in external page "Nature Chemistry".
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