Emerindanols A and B: Two Bipolyhydroindenol Sesterterpenes with 5/6–6/5 Coupled Ring System Discovered by Genome Mining

Genome mining of Emericella sp. XL-029 achieved a new type E sesterterpene synthase, EmES, which affored a novel bipolyhydroindenol sesterterpene, emerindanol A. Heterologous coexpression with the upstream P450 oxidase revealed C-4 hydroxylated product, emerindanol B. Notably, emerindanols A and B represented the first sesterterpenes featuring a unique 5/6–6/5 coupled ring system. EmES was postulated to initiate through C1–IV–V pathway and convert the fused ring intermediate into the final coupled ring product through a spiro skeleton.