Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering and his colleagues have developed a bacteria that is able to produce carminic acid, a natural red colorant, using metabolic engineering and computer-simulated enzymes. The bacteria strain is modified from Escherichia coli, and is able to synthesize carminic acid from glucose.

Carminic acid is usually harvested from cochineals, a scaled insect that primarily lives in Guatemala, Mexico, and the Canary Islands. It is used in products ranging from strawberry milk to lipsticks. However, carminic acid harvestation from insects sometimes results in protein contaminants, causing allergic reactions. Carminic acid is therefore not widely used, despite being one of the most natural and stable red colorants.

To synthesize carminic acid from E. coli, the research group first optimized the type II polyketide synthase machinery to produce flavokermesic acid, the precursor to carminic acid. A problem remained, however: the enzymes used to transform flavokermesic acid to carminic acid remained unknown. The team used biochemical reaction analysis to identify the enzymes converting flavokermesic acid to carminic acid, then enhanced the two identified enzymes using homology modeling and docking simulations. The final engineered E. coli strain was confirmed to produce carminic acid directly from glucose. Not only that, the modified C-glucosyltransferase (a membrane-bound protein responsible for carminic acid synthesis) created by the research team can be applied to other products, as demonstrated by the successful production of aloesin from the bacteria.

“The most important part of this research is that unknown enzymes for the production of target natural products were identified and improved by biochemical reaction analyses and computer simulation-assisted enzyme engineering,” Dr. Dongsoo Yang, a post-doc researcher from Professor Lee’s lab says. “Unknown or inefficient enzymes have always been a major problem in natural product biosynthesis, and here we suggest one effective solution for solving this problem. As maintaining good health in the aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” Professor Sang Yup Lee added.

This research was published in the Journal of the American Chemical Society, under the title “Production of carminic acid by metabolically engineered Escherichia coli”. The research was supported by the Novo Nordisk foundation in Denmark, the National Research Foundation of Korea, and the KAIST Cross-Generation Collaborative Lab Project.