Sweeter way to make drug precursor

Related tags Fatty acid Dna Protein Metabolism

Scientists have started to develop what could be a biosynthetic
route to producing compounds that serve as precursors to a range of
industrial chemicals, including pharmaceuticals.

It has the advantage of using glucose as a starting point to produce organic and aromatic compounds, rather than benzene which while widely used is a known carcinogen and has harmful effects on the bone marrow. This toxicity means that benzene requires great care when handling to reduce operator exposure.

Huimin Zhao and colleagues from the University of Illinois at Urbana-Champaign in the US have used fatty acid biosynthetic pathway of Brevibacterium ammoniagenes​, a bacterium commonly found in the human intestinal tract, to produce triacetic acid lactone (TAL).

TAL can be chemically changed to phloroglucinol (1,3,5-trihydroxybenzene), a pivotal structure necessary for the synthesis of a variety of bioactive compounds, including anticancer drugs.

In a study published ahead of regular print publication in the Journal of the American Chemical Society​, Zhao et al​ detail their proposed biochemical mechanism, which allows the fatty acid synthase pathway (FAS-B) to use glucose to make TAL.

FAS-B is a primary metabolic enzyme with multiple functions, and it may be used to make many diverse value-added compounds, commented Zhao.

To accomplish their task, the researchers had to understand the various domains of FAS-B that are necessary for fatty acid synthesis. They used a variety of bioinformatics tools to analyse 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.

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

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