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Dec 1, 2010 (Vol. 30, No. 21)

Synthetic Bio Not Yet Ready for the Market

Lab-Designed Calls and Pathways Take Genetic and Metabolic Engineering to Next Level

  • iGEM

    Click Image To Enlarge +
    Jeff Tabor, molecular biology doctoral student at University of Texas at Austin, holds a bacteria-produced photo of an enlarged E. coli bacterium. [Marsha Miller/The University of Texas at Austin]

    Synthetic biology in theory is limited only by imagination and one’s persistence in developing a technical platform, notes Laura Dress, CEO of Bridge, a synthetic biology communications consultancy.

    “Synthetic biology does not have an end point, unlike sequencing a genome, which has a finite milestone. With synthetic biology, scientists can literally act as DNA ‘artists’, using nucleotides to paint, so to speak.”

    In those terms, “DNA art” has, in fact, moved from the realm of science fiction to feasibility, with such developments as those by undergraduate students participating in the annual iGEM (International Genetically Engineered Machine) competitions. Since 2003, with the first competition at MIT, the undergraduate synthetic biology forum has encouraged open sharing of DNA constructs and synthesis methods, with the concurrent goal of establishing a Registry of Standardized Biological Parts.

    The idea is to have an open platform of known genetic functions (essentially cassettes of gene functionality) that can be cleverly combined to render whatever feasible phenotypic results one might wish. For example, a University of Texas at Austin 2005 iGEM team constructed an E. coli strain with heterologous phytochromes to render a plate of bacteria that functioned as a pseudocamera: any pictorial image laid atop lawns of the bacteria would, after light exposure over time, be accurately reproduced, with each E. coli cell essentially acting as a lighted pixel, and the lawn as a whole properly depicting gradations of light and dark.

    Another team in 2006 engineered E. coli such that, during an exponential growth phase, it produced a wintergreen scent, and during stationary phase, a banana scent. A 2008 team developed a beer-producing strain of S. cerevisiae that co-produced the anticancer and anti-inflammation compound resveratrol, a plant compound found on the skins of grapes and in other plants.

  • iGEM 2010 Competition Results

    Slovenia, winner of the BioBrick Trophy: The team designed a new platform comprising a DNA-guided scaffold that could arrange various functional protein domains in a defined linear order. They designed chimeric violacein biosynthetic enzymes with added zinc finger DNA binding domains and showed that in the presence of a correct DNA program, the yield of violacein production could be improved sixfold and formation of side reaction product deoxychromoviridans could be suppressed.

    Slovenia submitted 151 parts to the registry, which can be leveraged with this DNA-guided platform for biosynthesis, building oscillators, characterizing DNA binding domains, etc. It also won awards for the Best New Application Area and Best New Engineered BioBrick Part or Device.

    Peking, 1st runner up: The team developed a strategy for heavy metal bioreporter and bioabsorbent engineering based on reverse-engineering principles.  Peking also won the Best Environmental Project award.

    BCCS-Bristol, 2nd runner up: The team created agrEcoli, a device based on modified E. coli bacteria that detects and signals the presence of nitrates. BCCS-Bristol also won the Best Food or Energy Project award.

    Finalists also included University of Cambridge, Imperial College London, and Delft University of Technology.

    Best Project awards were given in each of the following tracks: Health or Medicine (Tie between Washington and Freiburg Bioware), Information Processing (tie between ETHZ Basel and Tokyo Tech), Manufacturing (MIT), Foundation Advance (Paris Liliane Bettencourt), and Software Tool (USTC Software).

  • Practical Applications

    But while such possibilities for synthetic biology are impressive, in practical application the bioindustry is focusing on less glitzy functions to address basic consumer and industry needs.

    Bridge is currently working with Lumin, a company formed to expand on a 2006 iGEM team’s project. Lumin has engineered an E. coli strain for use in a handheld biosensor to detect the presence of arsenic in drinking water supplies in developing countries.

    Lumin’s platform combines a natural E. coli arsenic detoxification pathway with a portion of the well-known lactose metabolism system. The system is constructed such that various promoters act in concert to render the lac gene as a reporter that indicates the level of arsenic in water supplies according to the pH of the test solution.

    Verdezyne focuses on creating synthetic gene libraries instead of single-gene manipulations to introduce diversity of enzymatic function into metabolic pathways for large-scale industrial fermentations.

    “Enzymes from diverse sources show wide variation in kinetic properties that may not adequately predict their performance in a recombinant microbe, so rational selection of the best genes encoding a metabolic pathway still remains a challenge,” says Stephen Picataggio, Ph.D., CSO.

    “Furthermore, flux control is often distributed over several reactions in a pathway, so that amplification of any one gene does not necessarily increase pathway flux. Therefore, coordinated and balanced overexpression of multiple genes encoding a pathway is necessary to maximize productivity.”

    Earlier this year, the company reported proof of concept in production of adipic acid (a precursor to nylon) with the engineering of a feedstock-flexible yeast strain capable of utilizing sugar, plant-based oils, or alkanes. The company estimates that its platform could realize a 20% manufacturing-cost advantage over traditional petrochemical production of adipic acid.

    Verdezyne also entered a collaboration earlier this year with Lallemand Ethanol Technology, a producer of yeast for the biofuels industry, to develop and commercialize a high-yield ethanol-producing strain.

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