Toward Engineering Rhizopus for Fumaric Acid Production

4 TOWARD ENGINEERING RHIZOPUS FOR FUMARIC ACID PRODUCTION 

To be competitive in price, the production of bulk chemicals by biological means requires among others, the use of available, cheap, and metabolically acceptable raw material. These should allow for high productivity and final concentration of the desired metabolite. For simple and straightforward downstream processing, negligible formation of side products, and minimal use of other chemicals are important. 

The principal operating costs associated with fermentation processes of low value compounds are the costs of the fermentation substrate, which for fumaric acid amounts to about 50-55% of total production costs. The small differential that normally exists between substrate and the product prices is one of the major intrinsic limitations of commercial fumaric acid fermentation. The break-even price for production is dependent on the price that can be obtained for the product, compared to the price paid for the substrate. The current prices commanded by purpose-grown crops in most developed countries make it difficult for the fermentation route to compete economically. The use of lower value agricultural, industrial, and domestic wastes could help improve the economics but the variable nature of these types of materials makes them much less attractive as fermentation substrates. For the idealized case described by Gangl et al. (1990), substrate cost was 75% of the total cost, mainly due to reduction in equipment cost and also taking into account the higher productivity for formation of fumaric acid. 

The following factors are suggested to be taken into account to enable a fair comparison of the chemical and biological manufacturing alternatives 

To enable the biological route, the producing organism should be able to accumulate higher final concentrations of fumaric acid, at a lower pH, to simplify the 

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Toward Engineering Rhizopus for Fumaric Acid Production... 

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