Optimize flavonoid production through metabolic engineering.

Flavonoids are plant polyphenols most commonly known for their antioxidant activity. The flavonoid pathway leads to the formation of phenolic compounds that have several biological functions. Scientists at the State University of New York at Buffalo have developed novel production platforms for the biosynthesis of natural flavonoid molecules--isoflavones, flavanones, flavones, flavonols, catechins and anthocyanins--using well-characterized microbial species, such as Escherichia coli and Saccharomyces cerevisiae.

The novel production methodologies under development will allow flavonoid compounds to be produced at a significantly lower cost and at higher purity. This is because production through microbial platforms is easier. Microorganisms are easier to grow than plants in a controlled environment. This approach relies on renewable carbon sources as a feeding source--glucose. It is more economical since there are lower energy requirements as microorganisms grow at room temperature. There is no reliance on toxic catalysts and organic solvents.

The scientists can provide novel flavonoids that can be used in various food applications, such as functional foods with improved antioxidant properties. Since some flavonoids, such as anthocyanins and deoxyanthocyanins, are natural colorants, their efficient and economical production through microbial synthesis will allow their use as alternatives to synthetic dyes, which may have adverse health effects. It is important to note that some anthocyanins, unlike other natural dyes, have some unique coloration properties, such as blue and purple coloration, which are among the highly sought natural colors in the food industry.

The critical issue that the researchers are still working on is improving production yields to make the processes even more competitive and amenable to large-scale production. In addition, the scientists use their microbial strains to produce not only natural flavonoids but also non-natural derivatives that have unusual chemistry and properties. The researchers believe that both the natural compounds (some of which are extremely rare in nature, such as deoxyanthocyanins) and the non-naturals can have applications not only in the food but also in the pharmaceutical industry. In particular, the researchers are exploring the use of these compounds in the treatment of obesity and type II diabetes. They have already accumulated some evidence demonstrating the beneficial effect of some of the compounds in the treatment of these two chronic diseases.

The researchers' data demonstrate that yeast is a better biocatalyst for flavonoid biosynthesis, displaying in some cases a 10-fold higher production yield compared to prokaryotic E. coli. The scientists have optimized flavonoid biosynthesis in E. coli by increasing the intracellular pool of malonyl-CoA through various metabolic and protein engineering approaches. Malonyl-CoA is a coenzyme A derivative which plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Using the constructed recombinant strains, the scientists also have achieved the biosynthesis of two novel, unnatural flavonoid compounds with fluro and amino groups introduced at the 4' position of the B phenyl ring. The research is ongoing.

Further information. Mattheos Koffas, Department of Chemical and Biological Engineering, The State University of New York at Buffalo, 904 Furnas Hall, Buffalo, NY 14260; phone: 716-645-2911; fax: 716-645-3822; email: mkoffas@buffalo.edu.