Advanced Bioprocess Technologies

Problem/Opportunity

There is significant potential for the production of designer chemicals that can be manufactured in flexible, small-scale operations with minimal separation and at very low costs, if technologies can be developed to manufacture these chemicals using cell-free, enzyme-based systems. Argonne has identified opportunities to develop cost-competitive biobased chemicals technologies that integrate fermentation with novel chemical separations approaches.

Mark Donnelly, ER Division, examines protein gels as part of a multidivision
collaboration led by the Chemical and Biological Technology Section

Approach

Argonne and Genencor International, one of the world's largest enzyme companies, initiated a major National Institute of Standards and Technology/Advanced Technology Program (NIST/ATP) program to pursue both fermentation and biocatalytic-based approaches for chemicals production. Eastman Chemical and two other companies, Microgenomics and Electrosynthesis, were added to the Joint Venture team. The team embarked upon the third largest NIST/ATP program ever awarded ($31.3 million over 5 years). Ascorbic acid (vitamin C) was targeted for both fermentation and enzyme-based manufacturing approaches. Argonne's roles included identifying the metabolic pathways of the candidate organisms, identifying needed modifications, developing methods to obtain the genes for new enzyme variants, and developing methods to stabilize the enzymes. The project was initiated and led by the Chemical and Biological Technology Section but included two other Argonne divisions: Environmental Research (ER) and the Center for Mechanistic Biology (CMB) (Figure 1).

Results

Progress was made for both fermentation and biocatalytic-based ascorbic acid production systems. The team made significant improvements in developing a fermentation-based system integrated with chemical separations; that process will be further developed.

Argonne was able to elucidate the biosynthetic pathways and guide genetic modifications of the microorganism. Other accomplishments by the Argonne team included developing a novel method for extracting specific genes for key enzymes from environmental samples of unculturable microorganisms. As a result, the team identified novel enzyme variants with improved properties not found in any existing cultures. Methods were also developed to stabilize enzymes. Several limitations remain for the biocatalytic system approach. One of the major limitations is that expensive cofactors are required. Publications and patents on these research developments are in preparation.

Future Plans

The process for the production of ascorbic acid that resulted from this project has significantly improved economics relative to the existing chemical process and competing biological processes. Eastman and Genencor have announced plans to build a full-scale plant by 2003. The project is currently being completed and publications are being prepared. Argonne is continuing fundamental work on the limitations of biocatalytic systems in an ongoing internal project.