NEW YORK, Feb. 8 - Maxygen scientists have applied the company's genome-shuffling technique to speed the evolution of a commercially valuable bacteria, quickly creating a genetic variant that can produce large amounts of antibiotic, according to recently published research.
The scientists were interested in speeding up the recombination and selection process used to generate improved strains of bacteria and eukaryotic cells for commercial production. The traditional process, called strain improvement, can be slow and laborious.
In a report published in this week's Nature, Maxygen scientists report that they chose to work with Streptomyces fradiae, a bacterium that produces the commercial antibiotic tylosin. After one round of traditional mutagenesis and phenotyping screening, they used recursive protoplast fusion to create a "shuffled" pool of bacteria. Because a significant proportion of the progeny have genes from more than two parents, they predicted, the variability would be greater, as would be the likelihood of a new high-tylosin variant of the bacteria in the pool.
The researchers then repeated the screening and shuffling process and identified among that generation seven strains of the bacterium that produced up to nine times more tylosin than the initial strain. The entire process took about a year and required about 24,000 assays. By contrast, the traditional technique that Eli Lilly used to create the current commercial version of this bacterium required 20 years and roughly 1 million assays.
"[I]n most cases it has taken years or even decades to identify bacterial strains that can produce product at commercial scale," Alan Shaw, president of Maxygen's chemical business unit, said in a statement. "Maxygen has now shown that we can use our whole genome recombination technologies to potentially develop significant production improvements in a period of months."
According to the company, the same technique could be expanded from pharmaceuticals to fermentation and bioprocessing.
Maxygen is based in Redwood City, Calif. It is publicly owned.