Functional Plasticity of a Viral Terpene Synthase, OILTS, that Shows Non-Specific Metal Cofactor Binding and Metal-Dependent Biosynthesis.

OILTS is a viral class I terpene synthase found from the giant virus Orpheovirus IHUMI-LCC2. It exhibits a unique structure and demonstrates high plasticity to metal cofactors, allowing it to biosynthesize different cyclic terpene frameworks. Notably, while OILTS produces only (+)-germacrene D-4-ol with the most common cofactor, Mg, it also biosynthesizes a different cyclic terpene, (+)-cubebol, with Mn, Co, or Ni, presenting a rare instance of cofactor-dependent enzyme catalysis. This is the first report of (+)-cubebol biosynthesis, to our knowledge. In addition, OILTS can uptake Zn as a cofactor, which is uncommon among ordinary terpene synthases. These findings suggest that OILTS's functional plasticity may benefit the virus in diverse host environments, highlighting potential evolutionary implications.