Researchers at UCI’s Institute for Genomics and Bioinformatics (IGB) are using CODA Genomics’ patented gene-protein-production algorithms to tweak the genetic structure of the yeast strain. The $1.67 million collaboration, which began 1 Sep, is funded by CODA Genomics, an Orange County synthetic biology company, and a UC Discovery Grant that provides matching funds for innovative industry-university research partnerships.

CODA’s namesake technology (Computationally Optimized DNA Assembly) uses computer algorithms to design synthetic genes that self-assemble easily and generate protein reliably in large amounts. This allows genes that occur naturally in certain organisms to be re-engineered to meet the needs of different organisms. When applied to Saccharomyces, the technology modifies the yeast so it can manufacture enzymes to break down a wider variety of sugars.

There are a number of issues faced by designers of synthetic genes which code for proteins of interest. CODA’s founders discovered and patented a key mechanism whereby proteins could be engineered to express well and remain functional through the process of cloning a gene into a non-native organism.

The founders discovered that all living organisms contain over-represented adjacent codon pairs which cause translational pauses at the ribosomal level to regulate the amount and properties of protein translated from a given gene.

The presence of these pause signals is a universal phenomenon. The actual codon pairs used to encode pausing vary widely from organism to organism, so moving protein production into a new organism scrambles these signals. These in turn may cause unpredictable levels of protein expression and impaired protein function, such as lack of solubility, improper folding or other problems.  CODA Genomics owns a critical technology that allows better control over such pauses so that functional proteins can be produced in heterologous systems, a required part of protein-based drug research and production.

—CODA Genomics

Even when the yeast is producing the necessary enzymes, inefficiencies in its metabolic pathways can slow the process. Pierre Baldi, IGB director and one of the project’s co-principal investigators, is computationally optimizing key enzymes to increase their efficiency. With computer algorithms, he is engineering compatibility of these key enzymes with various co-factors.

The researchers believe the bio-engineered yeast could use 80-90% of the sugars in biomass for ethanol production, up from about 20 percent with current technologies.

While there currently are yeast strains that can make ethanol from biomass, the existing process is very expensive and inefficient. We’re trying to build a better yeast strain—one that can produce more ethanol from the same amount of biomass by breaking it down naturally.

—G. Wesley Hatfield, principal investigator, UCI professor emeritus and co-founder of CODA Genomics

The multidisciplinary research project involves UCI researchers in the schools of information and computer sciences, engineering and medicine, as well as researchers at CODA Genomics, which spun off in 2005 from UCI research.

Also involved in the multidisciplinary project are researchers from IGB’s Computational Biology Research Laboratory (CBRL) in the California Institute for Telecommunications and Information Technology, and the labs of professors Suzanne Sandmeyer (biological chemistry) and Nancy Da Silva (biochemical engineering).

CBRL scientists perform the computation, gene design and gene assembly of the yeast proteins using CODA’s technology. Sandmeyer, a yeast molecular biologist, inserts the proteins into the yeast genome, ensuring the enzymes’ stability and their ability to function. Da Silva, a chemical engineer, ensures that fermentation conditions are optimal to maximize ethanol production.

In July, CODA announced that it had secured $7 million in Series C financing. The round was led by OVP Venture Partners, with current investors including Monitor Ventures, Tech Coast Angels, and Life Science Angels also participating.

Resources:

• Gutman G. and Hatfield G.W. “Nonrandom Utilization of Codon Pairs in Escherichia coli”, The Proceedings of the National Academy of Sciences USA, 86:3699-3703. (1989).

• CODA Genomics publications list