Scientists at the Helmholtz-Zentrum für Infektionsforschung (HZI) in Braunschweig, Germany have achieved an important advance in better understanding metabolic pathways in bacteria and their use. Using computer models, the "System and Synthetic Biology" working group, headed up by Vítor Martins dos Santos, calculated the genetic changes that are necessary for increasing the production of biosynthetics in the Pseudomonas putida bacteria. Experiments in the laboratory subsequently confirmed the results. With this, the creation of natural synthetics could be increased in a targeted manner in the future. The well-known science magazine, "PLoS Computational Biology" published the results today.
Pseudonomads are bacteria that occur everywhere in our environment. Their changeable and flexible metabolism makes it possible for them to live in different habitats, in water, in soil, on plants and in animals. Among these pseudonomads, there are exponents that can be used in biotechnology. These include Pseudomonas putida: It produces chemicals, pharmaceutical products, degrades waste and toxins. It also plays an important role in manufacturing high-quality substances for industry.
Now, in cooperation with a working group at the Virginia University in America, the researchers working with Martins dos Santos searched for possibilities of increasing the production of natural materials in P. putida. For this, they chose the chemical compound, polyhydroxy butanoic acid (PHB): It is one of the important biosynthetics, which could play a major role in medicine and industry in the future. From it, seam materials, screws, adhesives or implants can be created, which dissolve after an operation or biodegradable packaging. In order to increase the yield of PHB in P. putida, the researchers developed a mathematical model.
However, the path toward such a model is long and drawn-out. "When sequencing the genome of an organism, you frequently do not know what the individual genes mean and how their interaction functions", says Martins dos Santos. Based on computer models and knowledge from databases, the researchers created a network of individual genes and metabolic processes in P. putida. "All of this is similar to a map with cities and motorways", say, Jacek Puchałka, a colleague in Martins dos Santos' working group. "On some roads, there is a great deal of traffic, while others are very quiet. Some roads are blocked and then there are detours. The metabolic paths in P. putida behave in exactly the same way."
The researchers took advantage of the ability of bacteria to divert their metabolic paths, if a path is disrupted by mutations. The computer model shows which paths need to be changed in P. putida, in order to increase the yield of PHB. This is important for industry: Currently, the production of PHB is still very long and drawn-out and really not justifiable against the oil-based synthetics. "In future, it will be possible to manufacture biosynthetics more efficiently in large quantities. An if we have made our contribution to this, we are very pleased", says Puchałka.
Puchalka J, Oberhardt MA, Godinho M, Bielecka A, Regenhardt D, et al. (2008) Genome-Scale Reconstruction and Analysis of the Pseudomonas putida KT2440 Metabolic Network Facilitates Applications in Biotechnology. PLoS Comput Biol 4(10): e1000210. doi:10.1371/journal.pcbi.1000210