Center for Biorenewable Chemicals

CBiRC is basing its multidisciplinary research on biocatalysis efforts on the fatty acid or polyketide biosynthetic pathway (Thrust 1) with a goal of enhancing microbial production through highly targeted biotechnologies (Thrust 2). Combining biocatalysis with chemical catalysis (Thrust 3) opens the door to the fatty acid or polyketide-based platform chemicals (examples include carboxylic acids, dienes, pyrones, branched and ring structures, ethers and esters, bi-functionals and multi-functional chemicals) at the heart of CBiRC’s vision. Together, these programs are delivering new concepts that will be evaluated in testbeds for the proof-of-concept needed to evaluate production potential. All of this will be assessed in terms of a holistic life-cycle assessment addressing both techno-economics and carbon renewability.

Biocatalysis efforts are focused on enzyme engineering, utilizing advances in structural biology and new biological diversity (see ThYme Database) with a goal of engineering enhanced microbial production. Chemical catalysis efforts are focused on innovative supporting technologies including hydrothermal stability with novel catalysts and new chemical technologies. These feedstock chemicals will form the basis for founding a vigorous biorenewable chemicals industry based on an emerging array of bio-based opportunities.

Thrust 1: New Biocatalysts for Pathway Engineering
CBiRC has assembled a world-class team of scientists that are well known for their work on fatty acid/ polyketide metabolism and metabolic engineering. The team is focused on the enzymes involved in Claisen condensation-based carbon-chain extension and chain termination with the aim of directing the process of fatty acid assembly in microbes.

The enzymes and proteins of interest include:

3-ketoacyl-ACP Synthase
Acetoacetyl-CoA
Acetyl-CoA/Propionyl-CoA Synthetase
Acyl-CoA Carboxylases
Methylketone Synthase
Thioesterases
Biocatalysts of the Acetyl-CoA Condensation
Fatty Acid Elongase
Biotin

Overview of technologies:

CBiRC will develop technologies for generating a series of biologically derived chemicals that will represent a new precursor landscape for producing commodity molecules or final chemical products. This landscape will be established via a new paradigm in combinatorial metabolism based on biocatalysts identified and characterized by Thrust 1 of CBiRC. These biocatalysts will be accessed from a wide variety of organisms that harbor different polyketide/fatty acid biosynthetic pathways. These metabolic processes offer flexible biochemical conversions that can reiteratively generate a homologous series of alkyl-chains, which carry different chemical functionalities at specific positions of the molecules. Theoretically, these metabolic processes can generate alkyl-chains that range from 3- to 18-carbon atoms; however, the initial focus will be on molecules that are of up to 6-carbon atoms. It is important to note that the focus of the work is not the synthesis of complex polyketides, but using the biocatalytic machinery of the polyketide/fatty acid pathways to produce smaller molecules.

Thrust 2: Microbial Metabolic Engineering
CBiRC has assembled a world-class team of scientists that are well known for their work on microbial metabolic engineering. The team is focused on developing microbial platform technologies with the aim of redirecting the process of fatty acid assembly. The team focuses on strain characterization and optimization combined with analysis of flux, bioinformatics, proteomics and metabolomics.

Overview of technologies:

While the discovery of new pathways for the synthesis of small molecules with novel structures is a critical first step, significant effort is still required to develop efficient microbial strains in order to produce these molecules in an economically viable manner. The focus of the microbial metabolic engineering thrust is thus to develop microbial platforms using a systems approach to produce small polyketide-based molecules by incorporating new synthesis pathways discovered from Thrust 1 at high yields, high rates, and high product titers. Specifically, the microbial production platforms will have the following properties:

Integration of new pathways into the production platforms Efficient pathway design to allow proper balance between cell growth and product formation Balanced carbon and co-factor flow Maintenance of robust performance even at high product titers Robust cell growth and address scale-up issues with industrial input.

Thrust 3: Chemical Catalyst Design
CBiRC has assembled a world-class team of scientists that are well known for their work on catalysis and catalyst engineering. The team is focused on developing chemical catalysis platform technologies with the aim of engineering perfected processes. The team focuses on selective catalysis and stability to create a catalytic toolbox.

Overview of technologies:

Catalytic reactions are typically controlled by chemical processes that take place at various length scales. Moreover, complex couplings can take place between these processes, leading to potentially synergistic effects. Accordingly, an understanding of such couplings is essential for “catalytic reaction synthesis,” which is the identification, development, and optimization of catalytic reactions for new applications, especially those applications that are not simple variations of known catalytic reactions, such as developing new catalytic reactions for production of chemicals and fuels from renewable biomass resources. Important couplings in catalytic reaction synthesis for biomass conversion are expected to be: (1) functional coupling at the active site level; (2) kinetic coupling between active sites in the same reactor; (3) chemical coupling between surface reactions and homogeneous reactions for liquid-phase processes; and (4) thermodynamic and transport coupling between multiple phases (e.g., gas, aqueous, organic liquid, and solid catalyst phases) in complex reactors.