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New genome sequences target next generation of yeasts with improved biotech uses

Metabolically, genetically and biochemically, yeasts (unicellular fungi) are highly diverse; more than 1,500 yeast species have been identified. Characteristics such as thick cell walls and tolerance of pressure changes that could rupture other cells mean yeasts are easily scaled up for industrial processes. In addition, they are easy to grow and modify and, with notable exceptions such as Candida albicans, most are not associated with human illness. While these capabilities can be used for a wide range of biotechnological applications, including biofuel production, so far industry has only harnessed a fraction of the diversity available among yeast species.

To help boost the use of a wider range of yeasts and to explore the use of genes and pathways encoded in their genomes, a team led by researchers at the US Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science User Facility at Lawrence Berkeley National Laboratory, conducted a comparative genomic analysis of 29 yeasts, including 16 whose genomes were newly sequenced and annotated. In a study being published this week in the Proceedings of the National Academy of Sciences (PNAS), the team mapped various metabolic pathways to yeast growth profiles.

Obtaining a complete genome of a microbe that is industrially important greatly stimulates research in the area. This is particularly true when the genomic sequence is accompanied by a high-quality annotation of the genes, and the JGI annotation pipeline is one of the best in the field. We can expect an explosive interest in yeast biology in the coming years.

—senior author Tom Jeffries, Professor Emeritus at University of Wisconsin, Madison

Yeasts (which belong to the kingdom Fungi) can use a wide range of carbon and energy sources, ranging from cellulosic (6-carbon) and hemicellulosic (5-carbon) sugars to methanol, glycerol, and acetic acid. Products include ethanol and other alcohols, esters, organic acids, carotenoids, lipids, and vitamins.

We sequenced these diverse genomes to expand the catalog of genes, enzymes, and pathways encoded in these genomes for producing biofuels and bio-based products we use in daily life.

—Igor Grigoriev, JGI Fungal Program Head and co-senior author

Sequencing these less-known yeasts and characterizing their metabolic pathways, added study first author Robert Riley of the DOE JGI, helps fill in knowledge gaps regarding the fungal enzymes that can help convert a wide range of sugars into biofuel. The well-known yeast S. cerevisiae, for example, ferments glucose, but not the full range of sugars found in plant biopolymers.

One of the newly-sequenced yeasts is Pachysolus tannophilus, which can ferment xylose, otherwise known as wood sugar as it is derived from hemicellulose, which along with cellulose, is one of the main constituents of woody biomass. It is only distantly related to well-studied xylose fermenters such as Scheffersomyces stipitis—another yeast sequenced by the DOE JGI.

These distances are huge.

We might think of yeasts as simple unicellular, creatures similar to each other, but in fact their genetic diversity is like the difference between human and invertebrate sea squirt. We sequenced these diverse genomes to discover and facilitate the next generation of biotechnological workhorse yeasts for producing the fuels and products we use in daily life. We also discovered a genetic code change that, if not understood, will impede the yeasts’ biotechnological use.

—Robert Riley

In P. tannophilus, the team found a change in one of the three-letter codons that represent one of the 20 regularly used amino acids. That change from CUG-Ser to CUG-Ala is only the second observed case of a non-stop codon reassignment (a change from one amino acid to another, rather than from one amino acid to a stop codon) in nuclear genomes.

The CUG-Ala reassignment is important to biotechnology because in order to express novel biotechnologically useful genes from diverse yeasts into workhorses like Saccharomyces, we need to know if the yeasts’ genetic codes are the same. If they aren’t, expressing the novel genes won’t work because the proteins will be incorrectly translated.

—Robert Riley

DOE’s Office of Science is the largest supporter of basic research in the physical sciences in the United States.

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