Enhanced isoprenoid production in Escherichia coli cells harboring the archaeal mevalonate pathway

Microbial production of isoprenoids has attracted interest as a white biotechnology approach that yields valuable compounds, such as medicinal, biofuel, and sustainable industrial materials. Enhancement of isoprenoid production in microbial cells has been achieved through metabolic engineering, usually by exploiting one of the biosynthetic pathways supplying the precursors for isoprenoids, i.e., isopentenyl diphosphate and dimethylallyl diphosphate. The pathways used include the naturally occurring mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, and the artificial isoprenol/prenol utilization pathway. Among them, the introduction of the MVA pathway has been extensively studied and has actually been used to enhance the isoprenoid productivity of bacteria that intrinsically exhibit the MEP pathway, such as <i>E. coli</i>. A recently discovered, modified MVA pathway conserved in major archaea is distinguished from the other, canonical and modified, MVA pathways because it consumes two thirds of the ATP molecules that the other MVA pathways require. Based on this energy-saving nature, the archaeal MVA pathway can be exploited in metabolic engineering to produce valuable isoprenoid compounds. In this study, the archaeal MVA pathway was expressed in engineered <i>E. coli</i> cells, and its effects on the productivity of isoprenoids, such as lycopene and β-farnesene, were evaluated. This pathway was shown to function in aerobically grown <i>E. coli</i> and included an oxygen-sensitive enzyme. Moreover, the archaeal MVA pathway enhanced isoprenoid productivity in <i>E. coli</i> to a level comparable to that of the canonical eukaryotic MVA pathway under oxygen-limiting conditions.