In parallel with the above efforts, several groups have sought to harness the power of terpene cyclases to biocatalytically access trans-syn-fused terpenoids. Since van Tamelen's landmark study on a cyclase from rat liver, several reports have demonstrated the feasibility of this approach. Virgil and coworkers were able to use an unnatural oxidosqualene derivative in an enzymatic polycyclization to access the isomalabaricane tricyclic core and more recently, a collaborative work by the Porco and Abe laboratories showcased the utility of several fungal cyclases in constructing unnatural meroterpenoids with unusual ring fusions from synthetic substrates. These demonstrations notwithstanding, the approach suffers from low material throughput arising from the inefficiency of the enzymatic reaction and the difficulty in obtaining large quantities of the membrane-bound enzymes.