Abstract
Terpenoids constitute the largest class of natural compounds and are extremely valuable from an economic point of view due to their extended physicochemical properties and biological activities. Due to recent environmental concerns, terpene extraction from natural sources is no longer considered as a viable option, and neither is the chemical synthesis to access such chemicals due to their sophisticated structural characteristics. An alternative to produce terpenoids is the use of biotechnological tools involving, for example, the construction of enzymatic cascades (cell-free synthesis) or a microbial bio-production thanks to metabolic engineering techniques. Despite outstanding successes, these approaches have been hampered by the length of the two natural biosynthetic routes (the mevalonate and the methyl erythritol phosphate pathways), leading to dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP), the two common universal precursors of all terpenoids. Recently, we, and others, developed what we called the terpene mini-path, a robust two enzyme access to DMAPP and IPP starting from their corresponding two alcohols, dimethylallyl alcohol and isopentenol. The aim here is to present the potential of this artificial bio-access to terpenoids, either in vitro or in vivo, through a review of the publications appearing since 2016 on this very new and fascinating field of investigation.
Highlights
Taxol, artemisinin, menthol, camphor, cholesterol, beta-carotene, and rubber are just a few very well-known names of terpenoids of some interest for humanity
The first report dealing with the use of purified enzymes to access terpenoids from C5 alcohols demonstrated that the combination of a phosphatase and an isopentenyl phosphate kinase (IPK) could generate DMAPP starting from dimethylallyl alcohol (DMAOH) [12]
This review summarized the recent development of the artificial terpene mini-path (TMP) tosynthesize terpenoids starting from DMAOH and IOH
Summary
Artemisinin, menthol, camphor, cholesterol, beta-carotene, and rubber are just a few very well-known names of terpenoids of some interest for humanity. Two mechanisms, called the mevalonate pathway (MVA) and the methyl erythritol phosphate (MEP) pathway together with glycolysis, convert glucose into the two five carbon atoms, universal precursors of terpenoids: dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) Both pathways involve an 18 enzymes cascade. If successful, the implementation of this new artificial pathway offers the possibility to decouple microbial growth (use of glucose or glycerol as carbon and energy sources) and terpenoid production (use of DMAOH and IOH as biosynthetic carbon), simplifying the process of optimization. The idea became true when four groups reported independently in 2019 [10,11,12,13] the capacity of a two enzymes cascade to generate DMAPP and IPP from DMAOH and IOH in order to produce, either in vitro or in vivo, various terpenoids. Simplified enzymatic access to DMAPP and IPP, as well as terpenoids, through the TMP
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