BIOTECHNOLOGY 61
Cells of Trichosporon oleaginosus yeast. Staining makes the lipid droplets of the cells visible
between its structure and function. Tis was previously not possible using classical biochemical methodologies. “Tis approach is very
further: molecular-mechanical computer simulations allow them to decipher the individual steps in which a specific class of enzymes produces bioactive natural products. Tese include precursor stages of the cancer medication Taxol. Employing only computer simulation, Brück and his team correctly predicted, for the first time ever, all intermediate stages in the complex cascade of reactions that take place in the presence of this enzyme. In this manner they elucidated the enzyme’s precise mode of action, as well as the relationship
promising because using computer simulation we can change enzymes in a targeted manner and predict which products will be produced as a result,” says Brück. “If we then interconnect different enzyme activities with each other, we can even create new molecules that are not found in nature.” Te production of
cyclooctatin, a potent anti- inflammatory agent, provides a good example. Te scientists coupled a diterpene synthase enzyme with a new hydroxylase/ reductase enzyme complex in an Escherichia coli-based microbial production system provided for the production of trihydroxylated diterpene cyclooctatin. It was the in-silico discovery and experimental verification
of a new reductase/ferredoxin system derived from the recently published genome of Streptomyces afghaniensis, which enabled the scientists to raise the product yield by a factor of 43, compared with the native producer.
Faster development of new syntheses In the future, biotechnologists could adopt approaches similar to those deployed by engineers when they develop production steps for a new car. Making use of the synthetic biotechnology insight, they could put together a synthesis for new active agents using a chain of reactions with modified enzymes. Tis would greatly reduce the long and arduous process of ‘puzzling out’ new synthesis routes in the laboratory, as commonly applied today.
Te present research of
Brück’s research group was funded by the European
Community (ChiBio project), the German Federal Ministry of Education and Research (Advanced Biomass Value, SysBio Terp, OMCBP) and the German Federal Ministry of Economics (Bio@Jet project), as well as the Bavarian Ministry for Science (Algenflugkraft), the Bavarian Ministry of Economics (Algenflugkraft and sustainable production of bioinsecticides) and the Bavarian Ministry of the Environment (geo- biotechnology and PHB). Due to the enormous
potential of these methodologies, the TUM created a new teaching and research focus, Synthetic Biotechnology, in May 2016. Te Werner Siemens Foundation is funding the setup of the new research focus to the tune of €11.5 million.
For more information visit
www.tum.de
www.scientistlive.com
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