Chemoenzymatic Synthesis of Structurally Diverse Terpenoids from Farnesyl Pyrophosphates Modified at the Central Alkene Unit

TL;DR

Scientists used enzymes to create new terpenoids from modified FPP, including a pheromone used by cockroaches to attract mates.

Contribution

The study reports the enzymatic production of 18 new terpenoids, including a pheromone intermediate, using modified FPP derivatives.

Findings

Eight STSs were used to process three modified FPP derivatives, resulting in 18 new terpenoids.

One of the new terpenoids is a known intermediate in the synthesis of the cockroach pheromone periplanone B.

The study demonstrates a formal chemoenzymatic synthesis of the pheromone periplanone B.

Abstract

Sesquiterpene synthases (STSs) enable cationic cascade
reactions
with farnesyl pyrophosphate (FPP) resulting in an immense variety
of oligocyclic sesquiterpenes. Their substrate promiscuity allows
access to new sesquiterpene carbon skeletons. We explored the ability
of eight STSs to process three distinct synthetic FPP derivatives
modified at the central isoprenyl unit. These include the incorporation
of a keto group at C7 (“keto”-FPP), the relocation of
the olefinic double bond into the methyl group (“iso”-FPP),
and the shift of the double bond toward the aliphatic terminus of
the FPP backbone and loss of the methyl group at C7 (“nor-iso”
FPP). We report the enzymatic production of 18 new terpenoids, including
a large variety of new oxaterpenoids. One of these is known as a late
stage intermediate in the total synthesis of the sex pheromone periplanone
B, which is secreted by females of the American cockroach Periplaneta americana to attract mates. Thus, a formal chemoenzymatic
synthesis of this pheromone is disclosed.

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