March 2013

New meets old

The many applications
of biochemistry and molecular biology

Biochemistry and molecular biology are tremendously applicable to medicine. It is easy to lose sight of the fact that our sciences also underlie important applications in other fields. Much of this applicability stems from the tremendous similarity, at the molecular level, of all organisms, even those that on a macroscopic or even cell biological level seem quite disparate. This insight appears to have been articulated first in 1926 by the Dutch microbiologist A.J. Kluyver and his assistant H.J.L. Donker in their paper “Die Enheit in der Biochemie” (“The Unity of Biochemistry”) (1). This paper posited that all life forms depend on shared metabolic needs and processes. The subsequent elucidation of key common biochemical pathways, including the urea cycle (1932), the citric acid cycle (1937) and the glycolytic pathway (1940), revealed the power of this insight clearly. Our understanding of this commonality was amplified greatly by the discovery of the DNA double helix by James Watson and Francis Crick in 1953 (based largely on data collected by Rosalind Franklin). French biochemist (and one of the other founders of molecular biology) Jacques Monod summarized biochemical unity concisely in 1954 by saying, “What is true for E. coli is true for the elephant.”

The unity of all forms of life at the level of biochemistry and molecular biology is one of the most powerful insights in the history of human knowledge. This insight has enabled scientists to obtain results relevant to human biology and biomedicine from studies of model organisms including bacteria, yeast, worms, and mammals such as mice, although full translation of these results to humans is still challenging. Importantly, biochemical unity has tremendous implications for other fields of great importance, including energy, food and materials science. I will consider examples from each of these fields.

One of the great challenges of our time is finding sustainable sources of energy. The Earth is constantly bathed in light from the sun, and this presents both challenges and opportunities. One challenge takes the form of global warming caused by increasing concentrations of carbon dioxide and other greenhouse gases in the atmosphere that trap energy from the sun in the form of heat. How can carbon dioxide be removed from the atmosphere? Plants and some microorganisms use an intricate biochemical pathway to fix carbon dioxide from the atmosphere, presenting an opportunity for a solution. This pathway is initiated by the enzyme ribulose-1, 5-bisphosphate carboxylase/oxidase, or RuBisCO, which couples carbon dioxide to ribulose 1,5-bisphosphate to form two molecules of 3-phosphoglycerate. The ultimate products of the Calvin cycle are carbohydrates that can be utilized for a variety of purposes. Some potential methods to reduce greenhouse gases involve using plants or devices based on RuBisCO (ideally with improved catalytic efficiency derived through molecular biology techniques) to capture carbon dioxide.

Another energy challenge is developing sources of energy that are economically viable and do not produce large quantities of greenhouse gases. Again, observations in plants and microorganisms provide some key opportunities. The energy needed to drive the Calvin cycle (in the form of ATP and NADPH) is provided by the light reactions of photosynthesis. The most essential step in these reactions is a photo-induced electron-transfer reaction that converts absorbed light energy into oxidized and reduced species that then can be used to drive other reactions. Understanding this process has stimulated much research on solar-energy conversion, and the principles of biological electron transfer that have come out of studies of photosynthesis have had great effects of many aspects of chemistry and biochemistry.

Photosynthetic organisms also play a major role in most solutions related to increasing the available food supply as the human population continues to grow, because these organisms can use energy from the sun to produce carbohydrates. Of course, carbohydrates are not the only components needed for food; nitrogen-rich compounds such as proteins also are required. Fortunately, some plants, such as soybeans and other legumes, have evolved symbiotic relationships with nitrogen-fixing bacteria in the soil. Such bacteria produce the enzyme nitrogenase, which catalyzes the remarkable cleavage of the triple bond in nitrogen gas to produce two molecules of ammonia. The partnership between plant and bacterium depends on a complicated biochemical conversation featuring flavonoids secreted by the plants and lipochitooligosaccharide nodulation factors produced by the bacteria. This is but one example of the intricate chemical interactions and negotiations that take place throughout the microbial world.

Our world has been transformed by microprocessors and other devices produced by forming structural features on micrometer or submicrometer scales within macroscopic materials such as silicon wafers. The top-down approach for materials construction can be complemented through a bottom-up approach in which individual molecules are designed and constructed so that they self-assemble into desired shapes on the scale of tens to hundreds of nanometers. The concept of molecular nanotechnology has been articulated for more than 30 years (2), but recently some of the key steps in this process have been realized after decades of detailed studies of protein structure and folding. Individual proteins with preselected structures have been designed, synthesized and characterized (3) as have self-assembling protein oligomers (4). Molecular nanotechnology is still in its infancy, and it will be exciting to watch the anticipated developments as biochemists and other scientists push this frontier forward.

The unity of biochemistry first articulated nearly a century ago formed the basis for “A New Biology for the 21st Century,” a report from the National Research Council released in 2009 (5). This report explored how biology, unified by commonalities at the level of biochemistry and molecular biology and the associated analytical and synthetic methods that underpin these studies, could be harnessed to address sustainable food production, ecosystem restoration, optimized biofuel production and improvement in human health. The report calls for greater integration across traditionally separate disciplines within biology as well as close collaborations with physical, computational and earth scientists and with mathematicians and engineers. Because of the central role of biochemistry and molecular biology, American Society for Biochemistry and Molecular Biology members in particular are well-positioned to contribute to and, indeed, lead these crucial efforts. The “New Biology” report did not lead to much action, in large part because its publication coincided with the financial crisis. However, as we move forward, we should be sure to articulate the wide range of important societal issues that could benefit from biochemical and molecular biological insights and technologies.
 

REFERENCES
  1. 1. Kluyver, A. J. and Donker, H. J. L. Chem. Zelle Gewebe 13, 134 – 190 (1926).
     
  2. 2. http://www.pnas.org/content/78/9/5275.full.pdf
     
  3. 3. http://www.nature.com/nature/journal/v491/n7423/pdf/nature11600.pdf
     
  4. 4. http://www.sciencemag.org/content/336/6085/1129.full.pdf
     
  5. 5. http://www.nap.edu/catalog.php?record_id=12764
     
     

Photo of Jeremy BergJeremy Berg (jberg@pitt.edu) is the associate senior vice-chancellor for science strategy and planning in the health sciences and a professor in the computational and systems biology department at the University of Pittsburgh.
 
 
 
 


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1 Comments

  • I very much enjoyed your "Kluyver" article. Most beginning biochemistry students take the "Unity of Biochemistry" pretty much for granted, although they would never recognize that their, or their professor's, choice of an organism for study depends on incidental properties that have nothing to do with this Unity. You might be most interested in a long paper of mine: From "Butyribacterium" to "E. coli", An Essay on Unity in Biochemistry, Perspectives in Biology and Medicine, 47, 47-66 (2004). Some people did not like it, since it did not praise Monod to the heavens, but many agreed.

    I am almost 86, and would love to hear from you.

    Kind regards,

    Herbert

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