Xylome News Release, Madison, Wisconsin – Sept 20, 2016
Xylome Corporation was awarded $750,000 to develop a “Novel bioprocess for lipid production from industrial byproducts”. The two-year grant for $750,000 will start on October 1, 2016 and run through September 30, 2018.
The purpose of this Phase II project is to produce economically the next generation of sustainable, renewable, clean burning, high energy density, transportation biofuels. The proposed technology once successfully developed will enable existing biofuel producers to reduce their costs while increasing the value and diversity of their byproducts. It will convert their industrial waste products into tailored fatty acids suitable for biodiesel.
The technology will be compatible with and complementary to cellulosic ethanol producers, and it could potentially double the amount of biodiesel produced in the U.S. today. The 227 domestic ethanol plants range in size from less than 50 to more than 150 million gallons, and they have a total annual capacity of 15 billion gallons. Every gallon of ethanol also yields 1.9 pounds of soluble organics that must be evaporated or disposed. Xylome’s technology has the potential to convert half of this stream into biodiesel and to expand biodiesel production further with cellulosic feedstocks. By converting a larger fraction of the soluble cellulosic and hemicellulosic sugars along with fermentation byproducts, Xylome will increase the efficiency of existing ethanol plants and increase biofuel production.
Xylome’s objectives in this Phase II research are to increase the rates of production, modification and release of fatty acids from non-conventional lipogenic yeast. Fatty acids have much higher energy density than ethanol, but similar specific energy yields. Fermentation of organics to lipids can potentially occur with efficiencies equivalent to ethanol production. Lipids normally accumulate under nitrogen limiting conditions after replication has stopped. They are not excreted from the cells so recovery does not require distillation.
In Phase I, Xylome scientists identified and over expressed genes that increase lipid accumulation by 1.2- to 2-fold under high nitrogen conditions. In Phase II, they will use mating, selection, screening and evolutionary adaptation to combine the best of these modifications. Xylome scientists have also targeted additional genes to modify and release fatty acids from the cell. Xylome plans to optimize lipid production both from a cellular level with metabolic engineering and from an engineering perspective through bioprocess design and cultivation conditions. Xylome will also engineer cells to use rapidly the complex mixture of soluble oligosaccharides, hemicellulosic sugars and fermentation byproducts. By applying advanced molecular techniques and synthetic biology, Xylome will open up new opportunities for sustainable biofuel production.
Xylome News Release – July 11, 2016
Yeasts are unicellular fungi that can convert sugars from agricultural residues into renewable fuels and chemicals. The best known and most widely used yeast, Saccharomyces cerevisiae, grows well on glucose and sucrose and produces ethanol from starch, but it does not use sugars such as xylose and cellobiose, which are the prevalent forms found in agricultural residues.
Thus, when corn grain or sugarcane is made into ethanol, most of agricultural biomass goes unused.
The natural environment, however, contains many more species of yeasts that have a wide range of physiological properties. Some of these, which are found in soil, plant exudates or associated with insects, will consume almost all of the sugars found in nature. They also make a wide range of products such as vitamins, lipids, antioxidants, carotenoids, lipids, flavor compounds and other useful organics.
Recently a team of scientists led by Thomas Jeffries, President of Xylome and Professor Emeritus at the University of Wisconsin – Madison, published a study in the Proceedings of the National Academy of Sciences that reported complete genomic analyses of 29 yeasts including 16 with newly sequenced genomes. None of these yeasts are used to make bread or beer, but they include novel species that consume methanol at high temperature, grow at low pH, tolerate high salt, low temperatures, or acetic acid.
Surprisingly a rare yeast sequenced in this study, Pachysolen tannophilus, was found to use a non-conventional codon system that substitutes alanine for leucine when a CUG codon is encountered. Xylome’s scientist, Christopher Calvey, confirmed this finding by developing a novel genetic transformation system for this yeast.
In the PNAS study, researchers reported that their “genome comparison enabled correlation of genes to useful metabolic properties and showed the synteny of the mating-type locus to be conserved over a billion years of evolution.” The research team concluded that this work “provides a roadmap for future biotechnological exploitations.”
Xylome scientists have started exploiting these findings by developing new transformation systems to genetically manipulate several of the most biotechnologically important species.
Thomas Jeffries, Madison Wisconsin – August 17, 2016
After more than seven years of planning, sequencing, annotation and analysis, a team of thirty-nine scientists led by Dr. Igor Grigoriev of the Department of Energy Joint Genome Institute and Prof. Thomas Jeffries of the University of Wisconsin – Madison have released their findings on the “Comparative genomics of biotechnologically important yeasts”.
Their paper, published today in the on-line version of the Proceedings of the National Academy of Sciences, describes the genomic sequences, physiological characteristics and evolutionary relationships of twenty-nine yeast genomes – sixteen of which were sequenced for this study.
Probably one of the most startling findings was that a highly unusual yeast, Pachysolen tannophilus, uses a non-conventional codon system in synthesizing proteins. When it encounters the codon CUG, which normally signals insertion of the amino acid leucine into the growing protein chain, it substitutes alanine instead. No one knows why P. tannophilus has evolved this trait,
The project started in 2010 when the three lead scientists, Dr. Clete Kurtzman of the USDA National Center for Agricultural Utilization Research in Peoria, Illinois, Prof. Meredith Blackwell of Louisiana State University and Prof. Thomas Jeffries of UW-Madison collaborated in a proposal to the DOE Joint Genome Institute in Walnut Creek, California.
They wanted to know how yeasts evolved from their ancient roots in filamentous fungi, and whether their diverse properties could be attributed to the occurrence and patterns of enzymes coded for in their genomes.
Yeasts are best known for only a few species. In fact the “sugar fungus” Saccharomyces cerevisiae” is used around the world for making bread, wine and beer. Of the 1500 to 1800 recognized species of yeasts, about twenty have properties that make them useful in producing beverages, foods, organic acids, lipids and flavors.
Some are involved in food spoilage and about three account for opportunistic infections in people who have compromised immune systems, diabetes or high blood sugar, but most yeasts are harmless or potentially beneficial.
Even though yeasts are by definition unicellular and most replicate by budding, they are highly diverse from biochemical and physiological perspectives. Collectively they use a wide range of carbon sources for growth and can grow over a range of temperatures, salinity and pH.
Discovery of the novel genome codon system was driven initially by a comparative analysis of the small RNA “handles” known as tRNA. These are attached to specific amino acids during protein synthesis and they provide a recognition site or “anticodon” to direct which amino acid should be inserted when translating messenger RNA (mRNA) into protein. When the JGI Scientist, Sajeet Haridas, compared the occurrence of leucine residues in highly conserved proteins, he found that in some yeasts, when the codon CUG appeared in the mRNA, the amino acid serine was inserted rather than leucine. This substitution of serine for leucine had been recognized for almost 30 years since first described by Kawaguchi et al. in 1989.
Surprisingly, however, in one yeast – P. tannophilus – instead of serine, alanine was inserted when a CUG appeared in the mRNA. This led Prof. Kenneth Wolfe and his team at University College in Dublin, Ireland to sequence proteins from P. tannophilus and compare them to the sequence of nucleotides coding for them. Sure enough, alanine popped up most frequently when CUG was in the mRNA. Dr. Chris Calvey of Xylome Corporation in Madison provided the final proof by showing that P. tannophilus could not properly translate drug resistance genes using the conventional CUG to Leu translation, but when some other codon for leucine was inserted, the gene was translated properly.
Innovative research designed to lower the cost of lignocellulosic biodiesel
Madison, Wisconsin – July 1, 2015
The National Science Foundation (NSF) awarded Xylome Corporation $150,000 for a Phase I Small Business Innovative Research (SBIR) grant to develop a Novel process for lipid production from industrial byproducts. The grant, which starts on July 1, 2015, will focus on metabolic engineering a yeast to produce fatty acids for biodiesel production.
The successful completion of this project will facilitate conversion of existing biofuel and biomass byproduct streams into useful commercial fatty acids while reducing processing costs. In the longer term, the technology could enhance production of higher value second-generation biofuels. Xylome’s proposed technology could produce approximately 1.2 million gallons of biodiesel/yr. worth about $4 million from the byproducts of a single 70 million gallon ethanol plant. Beyond sugars from byproduct streams of existing ethanol plants, Xylome’s technology platform could facilitate fatty acid production from cellulosic and hemicellulosic sugars serving as a feedstock for cellulosic biofuel production.
The first objective of this Phase I research project is to enable lipid production during growth. The second will be to relieve biological constraints. The project will alter regulation of genes that limit production and introduce pathways that expand capacity. Yeasts, and fungi synthesize lipid when given excess carbon and limiting nitrogen, but low levels of lipid synthesis occurs during cell growth. Normally lipid only accumulates in cellular vacuoles after cell division has stopped. This requires extended cultivation times, and the amount of lipid that can be formed is constrained by the cell volume. The proposed approach will overexpress the enzymes for lipid synthesis so that the engineered cells will produce oil during growth while maintaining high levels of metabolic activity. New pathways will be introduced along with processes that will enable continuous lipid recovery. These modifications should enable a) lipid production in continuous high-density culture, thereby overcoming inherent low rates of lipid synthesis, and b) continuous separation of lipid, thereby alleviating the need for cell harvest, rupture and extraction. Xylome plans to increase its staffing to take on the new NSF-sponsored project.
Move adds space, equipment, meeting rooms and support
Madison, Wisconsin – April 1, 2015
Xylome Corporation expanded its research space and acquired new equipment and facilities for microbiological and molecular biology research in its move to the University of Wisconsin Research Park. The addition of chemical and P-2 biocontainment hoods along with HPLC, additional incubator and shaker space, the MGE Innovation Center in UW Research Park provides substantial support with meeting rooms, high speed internet and the opportunity to interact with many other biotechnology companies.
Technology package covers unconventional yeasts for the production of biofuel, renewable chemicals
MADISON, Wis. – Xylome Corporation has reached a deal with the Wisconsin Alumni Research Foundation (WARF) that gives Xylome the right to develop and market unconventional yeasts for the production of biofuels and renewable chemicals from cellulosic and hemicellulosic feedstocks.
The licensing agreement covers several technologies, including: the genetic transformation of widely studied native xylose- and cellobiose-fermenting yeasts; highly effective sugar transporters; and mutations in key genes that enhance xylose metabolism. Also covered are metabolically engineered yeasts for the synthesis of ethanol and other products, and cultivation conditions that enable co-fermentation of glucose along with xylose and cellulosic sugars.
The vast majority of yeast metabolic engineering efforts are aimed at conventional brewing and bread-making yeasts, however, conventional yeasts do not use all the cellulosic and hemicellulosic sugars found in biomass, so they must be genetically modified. To get around this problem, Xylome has developed naturally occurring, non-GMO yeasts that natively ferment the sugars from cellulosic feedstocks.
At the same time, Xylome’s technology enables genetic modification of these non-conventional yeasts to synthesize novel products. By targeting non-conventional yeasts that use a wider range of low-cost feedstocks Xylome can start from yeast platforms that have higher native capacities for product formation. Therefore, Xylome’s non-GMO yeasts can be used to convert cellulosic sugars into biofuels and can be genetically modified for synthetic biology applications as well.
“These technologies, along with Xylome’s accumulated know-how and proprietary platform strains, constitute a solid foundation for commercial development of unconventional yeast technologies,” says Thomas Jeffries, president of Xylome Corp.
“The genetic and processing technologies covered under these agreements have already proven their worth in laboratory and pilot trials,” says Jeffries. “Xylome expects to conduct commercial trials, production and ongoing development for target markets in the U.S. and abroad. The strong native fermentation capacities of our non-GMO platform strains along with effective, flexible genetic tools create a very powerful combination.”
Xylome is currently working with several companies to evaluate low-cost feedstocks from cellulosic and other sources. Technology covered under the current agreement was developed in conjunction with the Great Lakes Bioenergy Research Center (GLBRC).
Xylome Corporation is a privately held biotechnology company based in Madison, Wisconsin, that specializes in the development and deployment of non-conventional yeasts for the fermentation of cellulosic, hemicellulosic and other low-cost mixed sugar sources to renewable fuels and chemicals. Xylome’s leadership has many decades of experience in yeast physiology, biochemistry, molecular biology, metabolic engineering, fermentation scale-up and bioprocess engineering. Xylome intends to provide highly effective bioprocess technologies to existing biofuel, feed and chemical producers in order to reduce their processing costs and increase byproduct valuations. Xylome is actively seeking collaboration with grain ethanol producers, potential suppliers of low-cost byproduct waste streams, pretreated substrates and hydrolysates.
The Wisconsin Alumni Research Foundation (WARF) helps steward the cycle of research, discovery, commercialization and investment for the University of Wisconsin–Madison. Founded in 1925 by Professor Harry Steenbock as an independent, nonprofit foundation, WARF manages more than 1,600 active patents and an endowment of $2.6 billion as it funds university research, obtains patents for campus discoveries and licenses inventions to industry. For more information, visit warf.org.
GLBRC is one of three Department of Energy Bioenergy Research Centers funded to make transformational breakthroughs that will form the foundation of new cellulosic biofuels technology. GLBRC is led by UW–Madison, with Michigan State University as the major partner. For more information on the GLBRC, visit www.glbrc.org.
Certain statements in this press release may constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements that are not purely statements of historical fact, and can sometimes be identified by our use of terms such as “intend,” “expect,” “plan,” “estimate,” “future,” “strive” and similar words. These forward-looking statements are made on the basis of the current beliefs, expectations and assumptions of the management of Xylome and are subject to significant risks and uncertainty. Investors are cautioned not to place undue reliance on any such forward-looking statements. All such forward-looking statements speak only as of the date they are made, and the company undertakes no obligation to update or revise these statements, whether as a result of new information, future events or otherwise. Although the company believes that the expectations reflected in these forward-looking statements are reasonable, these statements involve many risks and uncertainties that may cause actual results to differ materially from what may be expressed or implied in these forward-looking statements.
News story by Matthew Weaver of the Capital Press – August 26, 2016
Xylome’s development of native yeasts that use unconventional sugars has significant implications for farmers and the processing industries.
Molly Sequin, Business Insider – June 3, 2016
A novel yeast, Spathaspora passalidarum, readily converts sugars from agricultural residues into sustainable, renewable biofuels.
04 Jun 2016 Francisco Ferreira da Silva
Brazil’s on-line news Económico reported on Xylome’s development of native yeasts for fermenting agricultural byproducts.
April 26th, 2013 | Wisconsin Energy Institute