Fatty acid pathway, glucose produce triacetic acid lactone

Scientists at the University of Illinois at Urbana-Champaign have designed a potential roadmap to use a biosynthetic pathway taken from a common microorganism to produce compounds that could serve as precursors to explosives or components in everyday devices such as liquid crystal displays or anti-cancer agents.

In a presentation April 1 at the 227th National Meeting of the American Chemical Society in Anaheim, Calif., Illinois doctoral student Wenjuan Zha reported how the fatty acid biosynthetic pathway of Brevibacterium ammoniagenes, a bacterium commonly found in the human intestinal tract, was used for the first time with glucose – rather than petroleum or other chemicals from non-renewable resources – to produce triacetic acid lactone (TAL).

In a paper available online at the Web site of the Journal of the American Chemical Society in advance of regular print publication, Zha and colleagues elaborate on their proposed biochemical mechanism that allows the fatty acid synthase pathway (FAS-B) to use glucose to make TAL. TAL is an energetic precursor for TATB, an explosive that is much more stable and sensitive than TNT.

Subsequently, Zha said, TAL can be chemically changed to phloroglucinol, a pivotal structure necessary for the synthesis of a variety of bioactive and energetic compounds.

FAS-B is a primary metabolic enzyme with multiple functions, and it may be used to make many diverse value-added compounds, said Zha’s adviser Huimin Zhao, a professor of
chemical and biomolecular engineering and of chemistry at Illinois.

To accomplish their task, the researchers had to understand the various domains of FAS-B that are necessary for fatty acid synthesis. Zha described how she and her colleagues used a variety of bioinformatics tools, such as the Web-accessible Biology Workbench, to analyze the gene sequence of FAS-B and identify the key catalytic residues.

They discovered that if they disabled the ketoacyl-reductase domain by replacing a catalytically active residue with an inert one by site-specific mutagenesis, it became possible to produce TAL.

The project – funded by the Office of Naval Research and done in collaboration with John Frost, a professor of chemistry at Michigan State University – established that the FAS-B altering technique makes it possible to use the fatty acid biosynthesis route as an alternative to using benzene to produce aromatics and other organic acids, Zhao said.

Zhao’s team now is working to increase the productivity of TAL by way of directed evolution of FAS-B.

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