Researchers at The Center for Biorenewable Chemicals (CBiRC), an NSF-funded Engineering Research Center headquartered at Iowa State University, are studying multiple enzymes involved in the fatty acid and polyketide pathway, including: 3-ketoacyl-ACP Synthases, Acetoacetyl-CoA Synthetases, Acetyl-CoA/Propionyl-CoA Synthetases, Acyl-CoA Carboxylases, Methylketone Synthases, Thioesterases, Biocatalysts of the Acetyl-CoA Condensation, Fatty Acid Elongases, Biotin (cofactor). As part of this work, CBiRC is using data-mining techniques to find amino acid sequences and tertiary structures of members of the seven enzyme groups that make up the fatty acid/polyketide synthesis cycle and include them in a major database. The new constantly updated ThYme (Thioester-active enzYmes) database contains primary and tertiary structures, classified into families and clans that are different from those currently found in the literature or in other databases. Researchers are arranging these members into families unrelated to each other by sequence similarity. The families are grouped into clans related by tertiary structure and mechanism. Furthermore, the families are divided into subfamilies by differences in their sequences. This allows an intimate understanding how enzymes produced by different organisms having the same substrate specificities are related to each other. Using this database along with biochemical studies of enzyme kinetics and specificities allows CBiRC to visualize ways of selecting and even engineering novel optimized enzymes.
Collectively these studies are enabling CBiRC to drive the incorporation of novel enzymes into its metabolic engineering design engine and hence make new strains synthesizing novel fatty acid and polyketides in microbes. The projects bring together faculty from Iowa State University as well as the Salk Institute and the University of Michigan.
The fatty acid and polyketide pathway enzymes are important because they are the biological catalysts that synthesize the building blocks for novel bio-based chemicals. Thus CBiRC envisions that these enzymes, when appropriately engineered, will create a foundation for delivering an array of novel molecules having longer and shorter chains, branched and ring structures as well as more functionalized molecules. These biocatalysis efforts are focused on the fatty acid or polyketide biosynthetic pathway which will be combined with chemical catalysis to create an array of novel chemical intermediates (e.g., olefins, diols, dienes, branched and ring structures, ethers and esters). These chemical intermediates will be used in a new chemical industry to make an array of bio-based materials ranging from polymers to surfactants, food additives to cosmetics, adhesives to paints, coatings, dyes, sealants and specialty chemicals. CBiRC envisions multiple applications of these new bio-based materials, resulting in the displacement of today's petrochemical sources of such high-value materials.
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Center for Biorenewable Chemicals (CBiRC)
CBiRC believes the existing petrochemical supply chain can be transformed with key foundational intermediates that deliver an array of drop-in chemistry or similar functionality to existing fossil-carbon-based chemicals.
