The Terpene Mini-Path, a New Promising Alternative for Terpenoids Bio-Production

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.

Antileishmanial Activity and In Silico Molecular Docking Studies of Malachra alceifolia Jacq. Fractions against Leishmania mexicana Amastigotes

“…Plant secondary metabolites represent viable options for current treatments of infectious diseases. Notably, terpenes constitute the largest and most diverse group of phytoconstituents from diverse natural sources [ 35 , 36 , 37 ].…”

In vitro Applications of the Terpene Mini‐Path 2.0

“…cbut‐(2 E ‐6 E )‐Farnesol : cbut‐FOH was obtained by treatment of cbut‐FPP with phosphatase PhoN Xt [5] . Briefly, the recovered white solid of cbut‐FPP was hydrolyzed in a Tris‐HCl buffer (50 mM, pH 7.5) with 0.2 U/mL of purified PhoN Xt in a total volume of 1 mL (1.5 mL Eppendorf® tube, 800 rpm, 37 °C, 24 h).…”

Prenylation: A Critical Step for Biomanufacturing of Prenylated Aromatic Natural Products

“…DMAPP is first produced from acetyl-CoA via a seven-step MVA or an eight-step MEP pathway, which is followed by the C-5 elongation of isopentenyl pyrophosphate (IPP) to form longer prenyl donors. For sufficient supply of prenyl donors, a simplified two-step pathway, isopentenol utilization pathway (IUP), has been successfully constructed in MCFs with high potential for producing endogenous IPP and DMAPP. , The biosynthesis of aromatic acceptors commonly depends on the shikimate pathway, where the precursors phosphoenolpyruvate (PEP) and erythrose-4-phosphate (E4P) are converted to dehydroshikimate (DHS), followed by the generation of chorismate, and then flavonoids, HGA, DHNA, and other ANPs . Finally, aPTs are responsible for the prenylation step to produce PANPs by modifying ANPs with various prenyl donors.…”