Environmentally benign synthesis of aromatic compounds from D-glucose

As the 21st century dawns, alternative methods are being sought for the synthesis of aromatic compounds. Today, 98% of aromatic compounds are currently derived from petroleum. As petroleum supplies continue to be depleted, there will be a need to find alternative routes to these commercially important chemicals that are derived from renewable feedstocks, such as cellulose, hemi-cellulose, and starch. In this dissertation, alternative routes to p-hydroxybenzoic acid, hydroquinone, p-cresol, and phenol will be elaborated that not only originate with D-glucose, but also utilize environmentally benign processes.; p-Hydroxybenzoic acid is the starting material for a class of antimicrobial compounds known as parabens and is a common monomer in liquid crystalline polymers. Industrially p-hydroxybenzoic acid is synthesized using the Kolbe-Schmidt reaction in which phenol is carboxylated to p-hydroxybenzoic acid under harsh conditions. A series of recombinant Escherichia coli strains have now been constructed and evaluated for their ability to synthesize p-hydroxybenzoic acid. Constructs differed in the strategy used for the overexpression of chorismate lyase and also differed as to whether mutations were present in the host E. coli to inactivate other chorismate-utilizing enzymes. The maximum concentration of p-hydroxybenzoic acid synthesized was 12 g/L in a 13% (mol/mol) yield from glucose when E. coli JB161/pJB2.274 was cultured under fed-batch fermentor conditions. The toxicity of p-hydroxybenzoic acid towards E. coli metabolism and growth was also evaluated.; Hydroquinone is a fine chemical used in photo development and as an antioxidant. p-Cresol is used in the manufacture of phenolic resins and as the starting material for the antioxidant butylated hydroxy toluene. Environmentally benign syntheses of these molecules are elaborated in which microbe-synthesized phydroxybenzoic acid is converted to hydroquinone by either the fungus Phanerochaete chrysosproium or the yeast Candida parapsilosis . Using C. parapsilosis as a whole-cell biocatalyst, p-hydroxybenzoic acid could be converted to hydroquinone in a 48% isolated yield. Under different culturing conditions, P. chrysosproium can be used to reduce phydroxybenzoic acid to p-hydroxybenzyl alcohol. Hydrogenation of the resulting alcohol affords p-cresol in a 46% yield from p-hydroxybenzoic acid.; An environmentally benign synthesis of phenol, derived from glucose via shikimic acid intermediacy, has also been established. Phenol, the second largest volume chemical currently derived from benzene, is used in the manufacture of phenolic resins, bisphenol A, and a variety of other commercially important chemicals. The current microbial synthesis of shikimic acid is plagued by contaminating quinic acid formation. Quinic acid formation has now virtually been eliminated by replacement of the native E. coli DHQ dehydratase and shikimate dehydrogenase activities by the Nicotiana tobacum bifunctional AroD·AroE enzyme. Shikimic acid can now be synthesized in 34 g/L in a molar ratio to quinic acid of 30:1. Purified shikimic acid can then be converted to phenol in a 45% yield by heating an aqueous solution of the acid to the subcritical temperature of 350°C. The byproduct m-hydroxybenzoic acid can be decarboxylated to phenol in subcritical water in the presence of copper to yield an additional 6% yield of phenol. Overall, shikimic acid can be converted to phenol in a 51% isolated yield.