Design & Simulation / Reaction & Synthesis

Pioneer enzymes near debut

Jun 01, 2004

Diversa Corp., San Diego, a pioneer in "bioprospecting," is now scaling up its first commercial industrial enzymes — using recombinatorial techniques to express them in different strains of yeast. The company has entered into a long-term agreement with Fermic S.A. de C.V., a contract manufacturer in Iztapalapa, a suburb of Mexico City, under which the Mexican firm will produce the enzymes. Diversa hopes that annual sales of the enzymes will reach $100 million within four years.

Some of the new products would be FDA-regulated, and Diversa is developing active pharmaceutical ingredients in separate joint ventures with a number of companies. However, its commercial pipeline is currently focused on the industrial biotech market, says Patrick Simms, senior vice president of commercial process development and operations.

In a venture with Danisco, Copenhagen, Denmark, Diversa has already scaled up Phytase, an enzyme that helps degrade phytic acid in animal feed, so that the animals absorb phosphate more readily. Production of that enzyme is already proceeding in full-scale 90,000-L reactors at Fermic’s facilities, says Samun Dahod, Diversa’s director of commercial process development.

At Fermic’s facilities, Diversa is now entering the production phase for Quantum, another phytase enzyme, which the company submitted for FDA approval about a year ago. Quantum also will be used in animal feed. Scaleup is expected to begin once the compound is approved.

To improve scaleup and lead to a more robust manufacturing process, Diversa developed a novel supervisory process control system for the fermentation using algorithms to optimize glucose feed rates to the fermenter, and to control the concentration of methanol in the yeast culture. An online methanol sensor developed by Raven Biotech, Vancouver, British Columbia, was critical to achieving this control. So far, production yields have improved five-fold and costs have dropped by 75%, the partners say.

By Agnes Shanley, contributing editor