In work that could transform radically the ways in which many of these compounds are produced commercially, the UB researchers are genetically engineering microorganisms, such as E. coli, into tiny, cellular factories.
Several patents related to this work have been filed by UB. The team also is in discussions with companies in the U.S. and abroad.
First Wave Technologies, Inc., a technology development company based in UB's New York State Center of Excellence in Bioinformatics and Life Sciences, which is collaborating with the UB group, recently received a highly competitive Phase I Small Business Innovation Research (SBIR) grant from the National Science Foundation to focus on the biosynthesis of a popular group of flavonoids called isoflavonoids.
"Ultimately, we want to be able to take a designed E. coli off of the shelf and drop into it the enzymes that constitute a particular biosynthetic pathway in order to make exactly the product we want," said Mattheos A. G. Koffas, Ph.D., assistant professor of chemical and biological engineering in the School of Engineering and Applied Sciences and leader of the UB team.
The UB approach to synthetic chemistry addresses some of the major challenges in conventional industrial production of specialty chemicals.
Through the use of specially adapted bacteria, specialized enzymes and natural feedstocks, microbial biosynthesis reduces or eliminates the need for petrochemical sources, elevated temperatures, toxic heavy metal catalysts, extremes of acidity and dangerous solvents, Koffas said.
In addition, the natural enzymes the UB researchers are using can facilitate chemical reactions that are difficult to accomplish through conventional chemistry, such as chiral synthesis, glycosylations and targeted hydroxylations, common but challenging steps in many syntheses.
"We are finding out how we can actually 'train' microbial systems to produce high yields of chemicals to be used as pharmaceuticals and to make production processes more efficient, less expensive and more environmentally friendly," Koffas said.
As with any commercial endeavor, process efficiency is a critical concern, he noted.
In work published in Applied and Environmental Microbiology in June, Koffas and his colleagues produced about 400 milligrams of flavonoids per liter of cell culture, far above the next highest yield of about 20 milligrams per liter produced by other microbial synthesis efforts.
"We have done this by increasing the amount of precursor available and re-engineering the native microbial metabolism," he explained, adding that they have taken different approaches to identifying the pathways that lead to the biosynthesis of precursors for desired compounds.
"Further improvement of production yields are possible and various approaches are being pursued by our team at this time," he said.
Another major challenge for microbial biosynthesis is that the enzymes required for certain chemical steps have special requirements that the host cell cannot meet efficiently, Koffas said. In some cases, the enzyme needs to be re-engineered, while in others the host cell needs modification.
Koffas' lab recently achieved the functional expression in E. coli of P450 monooxygenases, enzymes that are used widely in nature, but are not readily expressed in most industrially important microorganisms.
"P450 is very important in the synthesis of natural products," said Koffas. "For example, both Taxol, the breast cancer drug that is currently produced from plant cultures, and artemisinin, the anti-malaria drug, have P450 enzymes in their biosynthetic pathways."
The Koffas lab has introduced ways to modify both the P450 monooxygenase enzymes and the host cell, thereby improving their yield of flavonoids.
Microbial biosynthesis methods also are making it easier to create analogs of existing drugs, as well as new molecules for a broad range of therapeutics.
The UB researchers are particularly interested in developing novel molecules that can be used to treat chronic diseases, such as type II diabetes and obesity.
They also are using the methods to produce specialty compounds, such as natural pigments, that could replace chemical dyes in food.
Koffas' goal is to employ these microbial synthesis methods for a wide variety of applications.
Flavonoids, which are of interest to pharmaceutical companies because of their antioxidant and anti-carcinogenic properties, are difficult to produce using currently available methods.
Microbial synthesis strategies also are being adapted by the UB researchers for the biosynthesis of other commercially significant classes of compounds, including vitamins, anti-cancer drugs, anti-parasitic drugs, dyes and food supplements.
The UB group is working on boosting yields further and hopes to achieve pilot scale production of flavonoids by the end of this year.
For further information on commercialization of this technology, please contact Mike Fowler, commercialization manager for bioinformatics and health sciences, in UB's Office of Science, Technology Transfer and Economic Outreach (STOR) at firstname.lastname@example.org.
For information on commercialization of SBIR-funded research on the biosynthesis of isoflavonoids, please contact Jack Daiss, technical director, First Wave Technologies at email@example.com.
Koffas's research has received funding from the National Science Foundation, UB's New York State Center of Excellence in Bioinformatics and Life Sciences and the Independent Research and Development Fund of the UB Office of the Vice President of Research.
The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. UB's more than 27,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
Ellen Goldbaum | EurekAlert!
Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology
Scientists generate an atlas of the human genome using stem cells
24.04.2018 | The Hebrew University of Jerusalem
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
24.04.2018 | Information Technology
24.04.2018 | Earth Sciences
24.04.2018 | Life Sciences