Mevalonate Pathway Promiscuity Enables Noncanonical Terpene Production

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 13C 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.