Discovery of a New Type of Terpene Synthase Coded by an Orphan Gene in a Giant Virus

Giant viruses are mysterious entities that exist at the boundary between living and nonliving matters. One of the major mysteries surrounding the giant viruses is the function of their genes. Many of these genes are orphan genes, meaning their homologs cannot be found in other taxa, making it difficult to predict their functions. In this study, we discovered that one such orphan gene from a giant virus encodes a terpene synthase involved in the biosynthesis of terpenoids, one of the largest families of natural products. Surprisingly, this newly identified terpene synthase is distinct from previously known terpene synthases in terms of both its amino acid sequence and protein structure. Thus, the identified enzyme is a new type of terpene synthase, and we designate it as a giant virus (GV)-type terpene synthase. Heterologous expression of one GV-type terpene synthase named GiaTPS revealed that it accepted (2<i>E</i>,6<i>E</i>,10<i>E</i>)-geranylgeranyl diphosphate (GGPP) as a substrate to produce a new cyclized terpene compound. Given the abundance of orphan genes in giant viruses, we expect that many new classes of enzymes will be found from the genome of giant viruses.