ArticleProceedings of the National Academy of Sciences of the United States of America2019
The isoprenoid alcohol pathway, a synthetic route for isoprenoid biosynthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed, 174 citations in OpenAlex.
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- Stable Isotopic Labeling of Dimethylallyl Pyrophosphate (DMAPP) Reveals Compartmentalization of Isoprenoid Biosynthesis during Sporulation inJournal of the American Chemical Society · 2025Article
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- Enhancement of Lycopene Biosynthesis Using Self-Assembled Multi-Enzymic Protein Cages.Microorganisms · 2025Article
- Systematic biotechnological production of isoprenoid analogs with bespoke carbon skeletons.Nature communications · 2025Article
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- Substrate-Multiplexed Assessment of Aromatic Prenyltransferase Activity.Chembiochem : a European journal of chemical biology · 2025Article
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- Yeast metabolism adaptation for efficient terpenoids synthesis via isopentenol utilization.Nature communications · 2024Article
- Substitute Yeast Extract While Maintaining Performance: Showcase Amorpha-4,11-Diene Production.Microbial biotechnology · 2024Article
- Engineering Escherichia coli via introduction of the isopentenol utilization pathway to effectively produce geranyllinalool.Microbial cell factories · 2024Article
- The utility of Streptococcus mutans undecaprenol kinase for the chemoenzymatic synthesis of diverse non-natural isoprenoids.Bioorganic chemistry · 2024Article
- Discovery of a terpene synthase synthesizing a nearly non-flexible eunicellane reveals the basis of flexibility.Nature communications · 2024Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The more than 50,000 isoprenoids found in nature are all derived from the 5-carbon diphosphates isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Natively, IPP and DMAPP are generated by the mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways, which have been engineered to produce compounds with numerous applications. However, as these pathways are inherently constrained by carbon, energy inefficiencies, and their roles in native metabolism, engineering for isoprenoid biosynthesis at high flux, titer, and yield remains a challenge. To overcome these limitations, here we develop an alternative synthetic pathway termed the isoprenoid alcohol (IPA) pathway that centers around the synthesis and subsequent phosphorylation of IPAs. We first established a lower IPA pathway for the conversion of IPAs to isoprenoid pyrophosphate intermediates that enabled the production of greater than 2 g/L geraniol from prenol as well as limonene, farnesol, diaponeurosporene, and lycopene. We then designed upper IPA pathways for the generation of (iso)prenol from central carbon metabolites with the development of a route to prenol enabling its synthesis at more than 2 g/L. Using prenol as the linking intermediate further facilitated an integrated IPA pathway that resulted in the production of nearly 0.6 g/L total monoterpenoids from glycerol as the sole carbon source. The IPA pathway provides an alternative route to isoprenoids that is more energy efficient than native pathways and can serve as a platform for targeting a repertoire of isoprenoid compounds with application as high-value pharmaceuticals, commodity chemicals, and fuels.
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