June 15, 2001 By tinkering with a single gene, researchers have weaned photosynthetic algae off their dependence on sunlight and engineered them to grow and thrive in darkness. This accomplishment, reported in the 15 June issue of the journal Science, could pave the way towards clean, efficient, and inexpensive production of microalgae, which are used in a variety of commercial applications.
Common microalgae products include fluorescent pigments used in scientific labeling, dietary supplements such as beta-carotene and the fatty acid DHA, which is essential for nervous system development in infants, and feed for farm-raised fish, shrimp, and other aquaculture products.
Since these single-celled aquatic plants depend on sunlight for their energy, they are typically commercially cultivated in large outdoor ponds. These pond "farms" have several drawbacks, however, that make it difficult to control the quality and quantity of their microalgae produce. Contaminants can invade the pond, daily and seasonal changes in light and temperature can make growth rates unpredictable, and the algae can shade each other after a certain point, restricting the available light.
To solve these problems, commercial producers would like to grow microalgae inside fermenters where the tiny plants could be monitored for maximum purity and productivity. This technique requires that the algae give up their photosynthetic ways and use glucose (or another carbon compound) as their primary energy source.
Since most microalgae are unable to make this switch on their own, the Science researchers gave the microalgae Phaeodactylum tricornutum a metabolic boost by introducing a gene that encodes a glucose transporter. The researchers experimented with a variety of glucose transporter genes from human red blood cells, a different microalgae species, and yeast to determine which transporter type might allow the algae to increase its rates of glucose uptake.
P. tricornutum cells transformed with either the human or microalgal glucose transporter gene increased their rates of glucose uptake over normal cells, while the yeast genes produced no detectable difference in glucose uptake. Unlike normal P. tricornutum, the engineered algae expressing the human transporter were able to grow in darkened fermenters at densities fifteen times that of sunlight-grown algae.
Along with increased yield, the engineered algae grown in the fermenters have another distinct advantage--protection from microbial contamination. "Eliminating contamination means that the algae can be produced at a high purity for pharmaceutical applications or dietary supplements," says Science co-author Kirk E.Apt of Martek Biosciences Corporation.
The Science authors say that their research "demonstrates that a fundamental change in the metabolism of an organism can be accomplished through the introduction of a single gene." They acknowledge, however, that a one-gene solution will probably be the exception and not the rule for future metabolic engineering projects. In the case of P. tricornutum, for instance, the researchers found that the complete cellular pathway for breaking down glucose was "preinstalled" in the microalgae, and the additional gene simply allowed the plant to take advantage of its own systems.
In a related article in Science, Gregory Stephanopoulos of Massachusetts Institute of Technology and Joanne Kelleher of George Washington University School of Medicine suggest that metabolic engineering is moving away from single gene modifications and towards alteration of several targets within a particular pathway. "My own suspicion is that it won't always be this simple," says Apt. On the heels of their success with P. tricornutum, however, the research team is already developing other commercially important microalgae that can be grown using fermenter technology.
The other members of the research team include L.A. Zaslavskaia and J.C. Lippmeier at Martek Biosciences Corporation, and C. Shih, D. Ehrhardt, and A.R. Grossman at Carnegie Institute of Washington. This research was supported in part by NSF and the Carnegie Institute of Washington.
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