We are finding out how we can actually train microbial systems to produce high yields of chemicals to be used as pharmaceuticals and to make production processes more efficient, less expensive and more environmentally friendly, Koffas said.
As with any commercial endeavor, process efficiency is a critical concern, he noted.
In work published in Applied and Environmental Microbiology in June, Koffas and his colleagues produced about 400 milligrams of flavonoids per liter of cell culture, far above the next highest yield of about 20 milligrams per liter produced by other microbial synthesis efforts.
We have done this by increasing the amount of precursor available and re-engineering the native microbial metabolism, he explained, adding that they have taken different approaches to identifying the pathways that lead to the biosynthesis of precursors for desired compounds.
Further improvement of production yields are possible and various approaches are being pursued by our team at this time, he said.
Another major challenge for microbial biosynthesis is that the enzymes required for certain chemical steps have special requirements that the host cell cannot meet efficiently, Koffas said. In some cases, the enzyme needs to be re-engineered, while in others the host cell needs modification.
Koffas lab recently achieved the functional expression in E. coli of P450 monooxygenases, enzymes that are used widely in nature, but are not readily expressed in most industrially important microorganisms.
P450 is very important in the synthesis of natural products, said Koffas. For example, both Taxol, the breast cancer drug that is currently produced from plant cultures, and artemisinin, the anti-malaria drug, have P450 enzymes in their biosynthetic pathways.
The Koffas lab has introduced wa
|Contact: Ellen Goldbaum|
University at Buffalo