Metabolic Engineering of the Shikimic Acid Pathway in Escherichia coli for Production of Derived Aromatic Compounds

The microbial production of aromatic compounds derived from various intermediates of the shikimic acid (SHK) pathway comprise a great diversity of compounds with relevant applications in pharmacy for the synthesis of antimicrobial, antiviral, and anticancer compounds, in the food industry, elaboration of cosmetics and fragrances, or as precursors of diverse polymers with different applications. In Escherichia coli as a bacterial biofactory model, the SHK pathway provides three critical precursors for the synthesis of various aromatic compounds: 3-dehydroquinate (DHQ), 3-dehydroshikimic acid (DHS), and chorismate (CHA). In this contribution, we describe the main metabolic pathway-engineering strategies in E. coli to overproduce relevant aromatic compounds derived from the SHK pathway: Improving the transport capacity of carbon sources like glucose, glycerol, or xylose, the increment of the availability of the central carbon metabolism intermediates phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P), precursors that feed the SHK pathway; the increased flux of PEP and E4P to the pathway; and the development of specific biosynthetic pathways for at least 15 aromatic compounds derived from the SHK pathway, including the creation of some de novo biosynthetic pathways for some cases. Applying some of these metabolic engineering strategies to specific genetic backgrounds of E. coli resulted in producing several target aromatic compounds with titers above 60 g/L. Finally, the relevance of the biotechnological production of these compounds as a sustainable alternative to chemical synthesis processes from fossil sources or the hydrolysis of plant biomass is discussed.