Biocatalytic syntheses of aromatics from D-glucose: renewable microbial sources of aromatic compounds

Chemistry is moving into a new era in which renewable resources and starting materials such as D-glucose will likely be prominent features of industrial chemical manufacture. The keys to this progress are the design, development, and use of microbial biocatalysts. Aromatic biosynthesis serves as a paradigm for how biocatalysts can be manipulated to achieve the yield, rate, and purity criteria central to chemical manufacture. A disproportionate amount of the metabolic carbon flow of the biocatalyst must first be directed into the common pathway of aromatic amino acid biosynthesis. This review describes ways of achieving this goal through the traditional strategy of manipulating the catalytic activity of the first enzyme in the common pathway, as well as the amelioration of limitations in the in vivo availability of common-pathway enzyme substrates. The inability of individual enzymes to convert their substrate to product fast enough to avoid substrate accumulation further impedes carbon flow through the common pathway. This review also discusses identification and removal of these rate-limiting enzymes. Finally, we examine the creation of heterologous biocatalysts and how biocatalysis could be integrated with traditional chemical transformations to expand the number of organic chemicals that can be synthesized from glucose.