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dc.contributor.authorRinaldi, Mauro A; orcid: 0000-0001-7087-1184
dc.contributor.authorFerraz, Clara A; orcid: 0000-0003-2628-8412
dc.contributor.authorScrutton, Nigel S; orcid: 0000-0002-4182-3500
dc.date.accessioned2021-07-23T16:16:10Z
dc.date.available2021-07-23T16:16:10Z
dc.date.issued2021-07-07
dc.identifierpubmed: 34231643
dc.identifierdoi: 10.1039/d1np00025j
dc.identifier.citationNatural product reports
dc.identifier.urihttp://hdl.handle.net/10034/625342
dc.descriptionFrom PubMed via Jisc Publications Router
dc.descriptionPublication status: aheadofprint
dc.description.abstractCovering: up to 2021Terpenoids are a diverse group of chemicals used in a wide range of industries. Microbial terpenoid production has the potential to displace traditional manufacturing of these compounds with renewable processes, but further titre improvements are needed to reach cost competitiveness. This review discusses strategies to increase terpenoid titres in Escherichia coli with a focus on alternative metabolic pathways. Alternative pathways can lead to improved titres by providing higher orthogonality to native metabolism that redirects carbon flux, by avoiding toxic intermediates, by bypassing highly-regulated or bottleneck steps, or by being shorter and thus more efficient and easier to manipulate. The canonical 2-C-methyl-d-erythritol 4-phosphate (MEP) and mevalonate (MVA) pathways are engineered to increase titres, sometimes using homologs from different species to address bottlenecks. Further, alternative terpenoid pathways, including additional entry points into the MEP and MVA pathways, archaeal MVA pathways, and new artificial pathways provide new tools to increase titres. Prenyl diphosphate synthases elongate terpenoid chains, and alternative homologs create orthogonal pathways and increase product diversity. Alternative sources of terpenoid synthases and modifying enzymes can also be better suited for E. coli expression. Mining the growing number of bacterial genomes for new bacterial terpenoid synthases and modifying enzymes identifies enzymes that outperform eukaryotic ones and expand microbial terpenoid production diversity. Terpenoid removal from cells is also crucial in production, and so terpenoid recovery and approaches to handle end-product toxicity increase titres. Combined, these strategies are contributing to current efforts to increase microbial terpenoid production towards commercial feasibility.
dc.languageeng
dc.sourceeissn: 1460-4752
dc.titleAlternative metabolic pathways and strategies to high-titre terpenoid production in
dc.typearticle
dc.date.updated2021-07-23T16:16:10Z


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