|Title||Mevalonate pathway promiscuity enables noncanonical terpene production|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Eiben C.B, de Rond T., Bloszies C., Gin J., Chiniquy J., Baidoo E.EK, Petzold C.J, Hillson N.J, Fiehn O., Keasling J.D|
|Type of Article||Article|
|Keywords||Biochemistry & Molecular Biology; biosynthesis; cloning; design; enzyme; escherichia-coli; expression; functional-characterization; HDMAPP; HIPP; homodimethylallyl pyrophosphate; homoisopentenyl; juvenile hormones; mechanisms; mevalonate pathway; propionate; pyrophosphate; synthase; Terpenes|
Lepidoptera (butterflies and moths) make the six-carbon compounds homoisopentenyl pyrophosphate (HIPP) and homodimethylallyl pyrophosphate (HDMAPP) that are incorporated into 16, 17, and 18 carbon farnesyl pyrophosphate (FPP) analogues. In this work we heterologously expressed the lepidopteran modified mevalonate pathway, a propionyl-CoA ligase, and terpene cyclases in E. coli to produce several novel terpenes containing 16 carbons. Changing the terpene cyclase generated different novel terpene product profiles. To further validate the new compounds we confirmed C-13 propionate was incorporated, and that the masses and fragmentation patterns were consistent with novel 16 carbon terpenes by GC-QTOF. On the basis of the available farnesyl pyrophosphate analogues lepidoptera produce, this approach should greatly expand the reachable biochemical space with applications in areas where terpenes have traditionally found uses.