posted on 2021-02-04, 01:13authored byHanan
L. Messiha, Karl A. P. Payne, Nigel S. Scrutton, David Leys
Conjugated alkenes
such as dienes and polyenes have a range of
applications as pharmaceutical agents and valuable building blocks
in the polymer industry. Development of a renewable route to these
compounds provides an alternative to fossil fuel derived production.
The enzyme family of the UbiD decarboxylases offers substantial scope
for alkene production, readily converting poly unsaturated acids.
However, biochemical pathways producing the required substrates are
poorly characterized, and UbiD-application has hitherto been limited
to biological styrene production. Herein, we present a proof-of-principle
study for microbial production of polyenes using a bioinspired strategy
employing a polyketide synthase (PKS) in combination with a UbiD-enzyme.
Deconstructing a bacterial iterative type II PKS enabled repurposing
the broad-spectrum antibiotic andrimid biosynthesis pathway to access
the metabolic intermediate 2,4,6-octatrienoic acid, a valuable chemical
for material and pharmaceutical industry. Combination with the fungal
ferulic acid decarboxylase (Fdc1) led to a biocatalytic cascade-type
reaction for the production of hepta-1,3,5-triene in vivo. Our approach provides a novel route to generate unsaturated hydrocarbons
and related chemicals and provides a blue-print for future development
and application.