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3.7.1.1.1 Isoprenoid Precursor Biosynthesis

DOI: 10.1055/sos-SD-216-00220

Quin, M. B.; Flynn, C. M.; Ellinger, J. J.; Schmidt-Dannert, C.Science of Synthesis: Biocatalysis in Organic Synthesis, (20153362.

Efficient biotechnological production of isoprenoids requires obtaining the highest possible in vivo flux of the universal isoprenoid precursor, isopentenyl diphosphate (3-methylbut-3-enyl diphosphate, 1) from its central metabolic precursors. Furthermore, isopentenyl diphosphate is chemically unstable and membrane-impermeable, meaning that its accumulation should be prevented by suitably high enzymatic conversion into more-stable downstream isoprenoid products such as terpenoids and carotenoids. Similarly, identification and prevention of toxic pathway intermediate accumulation is critical to achieving maximal isoprenoid yields, and has been the subject of extensive metabolomic analysis.[‌23‌,‌24‌] Finally, because isopentenyl diphosphate (1) is a universal metabolite, limiting endogenous isopentenyl diphosphate utilization for biomass or other side-products is also employed whenever possible, typically through pathway deletion or reduction through genetic engineering of the host organism.[‌25‌] This section summarizes the native isoprenoid biosynthetic pathways, while focusing on the most successful examples of isoprenoid biosynthetic pathway optimization to date, determined by the primary driver of process cost, and the final product concentration or titer.[‌26‌,‌27‌]

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