Bacteria Are Key To 'Green' Plastics, Drugs

Finding "green" methods to make key chemical intermediates likesuccinate is a high priority for the chemical industry. Greentechnologies use renewable resources like agricultural crops ratherthan non-renewable fossil fuels, and they produce less waste.

"Succinate is a high-priority chemical that the U.S. Departmentof Energy has targeted for biosynthesis," said process co-developerGeorge Bennett, professor and chair of the department of biochemistryand cell biology at Rice. "One reason for this is succinate's broadutility -- it can be used to make everything from non-corrosive airportdeicers and non-toxic solvents to plastics, drugs and food additives.Succinate's also a priority because some bacteria make it naturally, sowe have a metabolic starting place for large-scale fermentation."

The centerpiece of Rice's succinate technology is a mutant formof E. coli that makes succinate as it's only metabolic byproduct. Thebug contains more than a half-dozen genetic modifications. It wascreated over the past four years by the research groups of Bennett andcollaborator Ka-Yiu San, the E.D. Butcher Professor of Bioengineeringand professor of chemical and biomolecular engineering.

The technology is taking its first step from the lab to themarketplace this month with the start of industrial scale-up efforts inKansas. These efforts resulted from an $80,000 award from the SmallBusiness Innovation Research (SBIR) program of the U.S. Department ofAgriculture. Bennett and San are working with Manhattan, Kansas-basedAgRenew Inc., which just began testing how to use farm-grown productslike grain sorghum as feedstocks for the succinate-producing bacteria.

"We are very pleased for the opportunity to continue ourcollaboration with our colleagues from Rice and work to further thedevelopment and commercialization of the succinate technology," saidPraveen Vadlani, principal research scientist for AgRenew. "We areexcited about the prospects this project offers to meet a market needfor the benefit of both institutions and American agriculture itself.We also appreciate the support of the U.S. Department of Agriculturefor this work to create another high-value product from agriculture."

Many researchers are trying to create a succinate-producingbacterial mutant. They use biotechnology to either insert genes thatboost succinate production or delete genes that interfere with it. Thegoal is to maximize the rate -- the speed of the conversion -- and theyield -- the amount of succinate produced per pound of glucoseconverted.

Bennett and San's bug -- known only by the designation SBS550MG-- contains an ingenious bit of metabolic engineering that allows it toproduce succinate in two different ways. One method exists in wildstrains of E. coli and has been modified with the deletion of fourgenes, each of which codes for a protein that interferes with or limitsE. coli's ability to turn glucose into succinate. Bennett and Sanactivated a second pathway and stimulated production by adding genesfrom lactococcus bacteria and sorghum.

Each genetic pathway metabolizes glucose and produces succinatevia dissimilar chemical reactions. That means the two don't compete orinterfere with one another. In fact, Bennett and San designed the pathsto be complimentary, but even so, they were gratified to see how wellthe process worked once both paths were put in place.

"Our experiments in the laboratory have produced near-maximumyields, with almost all the glucose being converted into succinate,"said San. "The implementation was actually easier than we expectedbecause the cells did the balancing themselves."

Bennett and San said they will continue to refine the organism to produce higher yields and fewer byproducts.

The research at Rice University is funded by the National ScienceFoundation, while the USDA has supported related research withinAgRenew, Inc.