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Abstract
Acetyl-CoA is a key metabolite precursor for the biosynthesis of lipids, polyketides, isoprenoids, amino acids, and numerous other bioproducts which are used in various industries. Metabolic engineering efforts aim to increase carbon flux towards acetyl-CoA in order to achieve higher productivities of its downstream products. In this review, we summarize the strategies that have been implemented for increasing acetyl-CoA flux and concentration, and discuss their effects. Furthermore, recent works have developed synthetic acetyl-CoA biosynthesis routes that achieve higher stoichiometric yield of acetyl-CoA from glycolytic substrates.
Highlights
The rapid development of genetic and genomic tools allowed discoveries of the genes and enzymes associated with the production of industrially important chemicals
Overexpression of Pyruvate dehydrogenase (Pdh) complex has been thought to be difficult, its overexpression for increasing flux to acetyl-CoA has been applied to isoamyl acetate production in E. coli, which is a valuable ester that can be biosynthesized from the condensation of isoamyl alcohol and acetyl-CoA [16]
Most of the studies expressed pantothenate kinase from E. coli to increase acetyl-CoA, this study showed the pantothenate kinase from P. putida may be a better candidate
Summary
The rapid development of genetic and genomic tools allowed discoveries of the genes and enzymes associated with the production of industrially important chemicals. Methods and principles of metabolic engineering have enabled the modification and transfer of the pathways that associate with these genes to almost any organism of choice to produce chemicals for industrial purposes As these production pathways are optimized through both enzyme selection and engineering, the production is often limited by the availability of essential central metabolites. Intracellular acetyl-CoA in E. coli was reported with a concentration of 0.05–1.5 nmol/mg cell dry weight (CDW), corresponding to 20–600 μM [11] This situation makes it difficult for the production pathways utilizing enzymes with high Km for acetyl-CoA. CoA availability wassynthesized demonstrated pyruvate with an inevitable carbon loss, several pyruvate dehydrogenase bypasses were increase intracellular acetyl-CoA concentration. The bullet points listed in the gray area pyruvate an inevitable carbon loss, several pyruvate dehydrogenase were demonstrated show with the detail metabolic engineering method to meet each strategy.
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