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Polyketide Process Opens Up Opportunities

April 23, 2018
Bio-engineered approach could underpin commercial production of plastics and drugs.

A new sustainable method for making triacetic acid lactone (TAL) could turn it into a platform chemical for industrial-scale manufacture of a variety of products, say a team of researchers at The University of Texas at Austin (UT), Austin, Texas. Their synthesis approach provides output that far exceeds that of current bio-based routes to the polyketide, they note, enabling cost-effective production of TAL.

Polyketides are an important class of naturally derived molecules that already are used for making a variety of products such as nutritional supplements, specialty polymers, pigments and pharmaceuticals. For instance, pharmaceutical companies rely on polyketides now on the market to derive more than 20 drugs, including immunosuppressants, statins and antimicrobials.

Sustainable Plastic Production

Figure 1. UT engineers mold the new, sustainably produced plastic material into a Longhorn silhouette. Source: Cockrell School of Engineering, University of Texas at Austin.

Technical challenges have constrained current synthetic production of polyketides, limiting practical applications for consumer- and industry-based needs. Most technologies suffer from limited product yields, resulting in difficult chemical synthesis and poor economics.By rewiring metabolism in the yeast Y. lipolytica through synthetic biology and genetic engineering, the research team increased TAL production capacity tenfold, enabling mass production that can underpin a variety of industry applications.Using the new approach, the researchers were able to purify TAL directly from a bioreactor to make a new plastic material that can be formed into a film; it exhibits an orange hue and relative transparency. An article in the Proceedings of the National Academy of Sciences contains more detail on their research.“This work represents the development of a platform strain that can lead to new types of monomers. In reality, we have rewired this yeast cell to over-produce Type III polyketides generically. As a result, this same technology can be applied to a host of other known and novel molecules. Each of these molecules can have novel applications in the polymers, chemicals, and even fuels and pharmaceuticals space,” says Hal Alper, professor in the McKetta Department of Chemical Engineering in the Cockrell School of Engineering who led the research.UT’s technology commercialization office has filed a U.S. patent application on the technology and aims to secure worldwide patents. It is looking to industry to help with the broader process development and pilot-scale production. “We have started talking with commercial partners who are interested in the technology and continue to explore commercial applications for both the TAL molecule and the broader cellular platform we have created,” notes Alper.The team now is focused on enhancing the platform strain by identifying further genetic modifications that can increase the overall rate, titer, and yield of production. The researchers also are striving to diversify the type of monomers that can be produced.“We continue to work on increasing overall efficiency in our system and in pushing the boundary to new types of monomers that can be produced using our system. In doing so, coupling the biochemistry with polymer science offers a unique opportunity and challenge. Our goal is to bring novel, valuable products to the market much faster using this pre-engineered organism,” stresses Alper.“Bio-based solutions to specialty and commodity chemicals provide a unique opportunity for sustainable, green, and economically viable processes. Likewise, the merger of synthetic biology and materials/polymer chemistry provides a unique opportunity to expand the chemical industry,” he concludes.

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