Discovery and improvement of glyphosate tolerance gene

Verdia Inc., a wholly owned subsidiary of Maxygen, Inc. has announced today the publication in the journal Science of a study that describes the successful development of a novel glyphosate-resistant crop trait by scientists at Verdia and Pioneer Hi-Bred International, Inc., a wholly owned subsidiary of DuPont. The report details the use of Maxygen's MolecularBreedingTM directed evolution platform to develop enzymes exhibiting glyphosate N-acetyltransferase (GAT) activity that confer glyphosate tolerance to plants. This improvement in enzyme activity may provide an alternative strategy for supporting glyphosate use on major crops such as corn, soybean and cotton.

The study, entitled "Discovery and Directed Evolution of a Glyphosate Tolerance Gene," was performed by Verdia under the direction of Linda Castle, Ph.D., Product Development Group Leader at Verdia and senior author on the study. The study will be featured in the May 21, 2004 issue of Science.

Glyphosate is one of the most commonly used herbicides on many food and non-food crops. The value and importance of glyphosate stems from its effectiveness, low cost and low environmental impact. In 2002, the annual worldwide sales of glyphosate totaled $3.4 billion and global sales of herbicide-tolerant seed and traits was $2.2 billion according to Cropnosis Limited.

Scientists at Verdia used microbial diversity collections to discover a family of genes, called gat genes, exhibiting a very low level of the desired novel enzymatic activity. This activity was then improved using the MolecularBreedingTM directed evolution platform. Eleven iterations of DNAShufflingTM recombination resulted in nearly a 10,000 fold improvement in enzyme activity over the parental enzymes. The ability to improve enzyme activity using the MolecularBreedingTM directed evolution platform outpaced and outperformed traditional means to modify genes and proteins that typically attempt to predict sequence-function relations.

"The increase in activity would never have been possible to achieve using traditional technologies to improve genes such as random mutagenesis and rational design," said Linda Castle, Ph.D. "This demonstration of improved glyphosate tolerance should be applicable to many crops. Further, this study validates our ability to create novel commercial opportunities in crop protection and plant quality traits for ourselves and our partners."

"I am extremely proud of the scientific accomplishments that Maxygen and Verdia have made," said Russell Howard, Ph.D., Chief Executive Officer of Maxygen. "Our MolecularBreedingTM directed evolution platform continues to deliver success in creating valuable commercial properties in genes and proteins for novel business applications." http://www.maxygen.com/

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