Messiha, Hanan L, Payne, Karl AP 
ORCID: 0000-0002-6331-6374, Scrutton, Nigel S and Leys, David
(2021)
A Biological Route to Conjugated Alkenes: Microbial Production of Hepta-1,3,5-triene.
ACS SYNTHETIC BIOLOGY, 10 (2).
pp. 228-235.
Abstract
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 <i>in vivo</i>. Our approach provides a novel route to generate unsaturated hydrocarbons and related chemicals and provides a blue-print for future development and application.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | hepta-1,3,5-triene, 2,4,6-octatrienoic acid, conjugated alkene production, UbiD decarboxylase, andrimid biosynthesis, ferulic acid decarboxylase Fdc1 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 01 Feb 2023 11:20 |
| Last Modified: | 01 Feb 2023 11:20 |
| DOI: | 10.1021/acssynbio.0c00464 |
| Open Access URL: | https://doi.org/10.1021/acssynbio.0c00464 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3168066 |
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