Presidential Green Chemistry Challenge: 1998 Academic Award (Draths and Frost)

Dr. Karen M. Draths and Professor John W. Frost of Michigan State University

Use of Microbes as Environmentally Benign Synthetic Catalysts

Innovation and Benefits: Adipic acid, a building block for nylon, and catechol, a building block for pharmaceuticals and pesticides, are two chemicals of major industrial importance. Using environmentally benign, genetically engineered microbes, Dr. Draths and Professor Frost synthesized adipic acid and catechol from sugars. These two chemicals are traditionally made from benzene, a petroleum product; they can now be made with less risk to human health and the environment.

Summary of Technology: Fundamental change in chemical synthesis can be achieved by elaboration of new, environmentally benign routes to existing chemicals. Alternatively, fundamental change can follow from characterization and environmentally benign synthesis of chemicals that can replace those chemicals currently manufactured by environmentally problematic routes. Examples of these design principles are illustrated by the syntheses of adipic acid and catechol developed by Dr. Karen M. Draths and Professor John W. Frost. The Draths-Frost syntheses of adipic acid and catechol use biocatalysis and renewable feedstocks to create alternative synthetic routes to chemicals of major industrial importance. These syntheses rely on the use of genetically manipulated microbes as synthetic catalysts. Nontoxic glucose is employed as a starting material, which, in turn, is derived from renewable carbohydrate feedstocks, such as starch, hemicellulose, and cellulose. In addition, water is the primary reaction solvent, and the generation of toxic intermediates and environment-damaging byproducts is avoided.

In excess of 4.2 billion pounds of adipic acid are produced annually and used in the manufacture of nylon 6,6. Most commercial syntheses of adipic acid use benzene, derived from the benzene–toluene–xylene (BTX) fraction of petroleum refining, as the starting material. In addition, the last step in the current manufacture of adipic acid employs a nitric acid oxidation resulting in the formation of nitrous oxide as a byproduct. Due to the massive scale on which it is industrially synthesized, adipic acid manufacture has been estimated to account for some 10 percent of the annual increase in atmospheric nitrous oxide levels. The Draths-Frost synthesis of adipic acid begins with the conversion of glucose into cis,cis-muconic acid using a single, genetically engineered microbe expressing a biosynthetic pathway that does not exist in nature. This novel biosynthetic pathway was assembled by isolating and amplifying the expression of genes from different microbes including Klebsiella pneumoniae, Acinetobacter calcoaceticus, and Escherichia coli. The cis,cis-muconic acid, which accumulates extracellularly, is hydrogenated to afford adipic acid.

Yet another example of the Draths-Frost strategy for synthesizing industrial chemicals using biocatalysis and renewable feedstocks is their synthesis of catechol. Approximately 46 million pounds of catechol are produced globally each year. Catechol is an important chemical building block used to synthesize flavors (e.g., vanillin, eugenol, isoeugenol), pharmaceuticals (e.g., L-DOPA, adrenaline, papaverine), agrochemicals (e.g., carbofuran, propoxur), and polymerization inhibitors and antioxidants (e.g., 4-t-butylcatechol, veratrol). Although some catechol is distilled from coal tar, petroleum-derived benzene is the starting material for most catechol production. The Draths-Frost synthesis of catechol uses a single, genetically engineered microbe to catalyze the conversion of glucose into catechol, which accumulates extracellularly. As mentioned previously, plant-derived starch, hemicellulose, and cellulose can serve as the renewable feedstocks from which the glucose starting material is derived.

In contrast to the traditional syntheses of adipic acid and catechol, the Draths-Frost syntheses are based on renewable feedstocks, carbohydrate starting materials, and microbial biocatalysis. As the world moves to national limits on carbon dioxide (CO₂) emissions, each molecule of a chemical made from a carbohydrate may well be counted as a credit due to the CO₂ that is fixed by plants to form the carbohydrate. Biocatalysis using intact microbes also allows the Draths-Frost syntheses to use water as a reaction solvent, near-ambient pressures, and temperatures that typically do not exceed human body temperature.

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