Total Biosynthesis of Fungal Indole Diterpenes Using Cell Factories

Reconstitution of biosynthetic genes in a heterologous host is a newly emerging method for synthesis of fungal secondary metabolites.Application of this method to indole diterpenes is described.We have successfully elucidated all of the individual enzymatic steps and produced four representative indole diterpenes, paspaline, paxilline, aflatrem, and penitrem, at a yield of ~100 mg/L.These results confirmed that the Aspergillus oryzae expression system is highly reliable for elucidation of biosynthetic pathways, even those involving 17 enzymatic reactions.CONTENTS 1. Introduction 2. Expression system of biosynthetic genes in Aspergillus oryzae 3. Indole diterpenes produced by various fungi 4. Enzymatic synthesis of fungal indole diterpenes 4-1.Paspaline 4-2.Paxilline 4-3.Aflatrem 4-4.Penitrem 5. Conclusion