H. Feldmann on the Oldest Domesticated Organism: Yeast

H. Feldmann on the Oldest Domesticated Organism: Yeast

Author: Gregor Cicchetti and Vera Köster

Yeast is a single-celled, eukaryotic microorganism best known for its use in baking and for fermentation of carbohydrates to carbon dioxide and alcohol. In addition, yeast plays an important role as a model organism in modern molecular and cell biology and is one of the best characterized organisms in the world. As a model organism it has helped researchers to understand not only the biology of the eukaryotic microorganism but also multicellular organisms including humans.

Horst Feldmann, Professor at Ludwig-Maximilians University Munich, Germany, has extensively studied yeast, including their tRNA and protein biogenesis, yeast retrotransposons, mitochondrial genome, and yeast proteasome. He was a coordinator in the EU project “Sequencing and Analysis of the Yeast Genome”.

He talks to Drs. Vera Köster and Gregor Cicchetti, ChemViews magazine, about the history of yeast in the lab, why yeast is such an important organism, and the future of yeast research.

Yeast is one of the oldest domesticated organisms, and has been used in research for almost 100 years.

Indeed, the yeast, Saccharomyces cerevisiae, may be the oldest domesticated organism. Probably, its usage in baking bread and making alcoholic beverages about 8000 years ago started as an arbitrary achievement by some ancient cultures, and has been practiced ever since. When Antoni van Leeuwenhoek saw the first yeast cells in his microscope in 1680 it took nearly 200 years before Louis Pasteur recognized that fermentation is strictly associated with yeast metabolism.

So how long has yeast been used in the laboratory?

Knowledge about yeast physiology, sexuality, and phylogeny has been collected since the beginning of the last century. Yeast was also used as a source for production of chemical compounds. In the mid-1930s, yeast was introduced as an experimental organism. Many researchers realized that it offered an ideal system in which cell architecture and fundamental cellular mechanisms could be successfully investigated.

What makes yeast such an important organism?

Among all eukaryotes, yeast combines several advantages: It is a unicellular organism. It can be grown on well-defined media allowing complete control over environmental parameters, has a short propagation time, and can be used for mass production. Yeast is very well suited for classical and molecular genetic techniques. The ease of manipulation of yeast made many of the detailed functional studies with biochemical approaches possible.

Finally, with the deciphering of the complete yeast genome sequence in 1996, it became the first eukaryotic organism that could serve as a model system for systematic functional analyses, and a suitable reference for a multitude of eukaryotes. In fact, comparisons provided evidence that substantial cellular functions are highly conserved from yeast to mammals, including humans.

Your book Yeast – Molecular and Cell Biology is currently the only textbook on yeast. Isn’t that astonishing?

Some 20 years ago, multi-volume books on yeast genetics, biochemistry, and molecular biology were available. For example, Molecular and Cellular Biology of the Yeast Saccharomyces by Broach, Pringle, and Jones, and Guide to Yeast Genetics and Molecular Biology by Guthrie and Fink.

They were considered standard equipment in every yeast laboratory. Additionally, several monographies devoted to practical aspects were on the market. To the best of my knowledge, no compact textbook on yeast existed even at that time.

Unfortunately, none of the aforementioned authors or anyone else took the initiative to write or edit an up-to-date textbook. So, even after the Yeast Genome Project had been finalized an actual overview on yeast was missing.

What inspired you to write a book about yeast?

For myself, working in the yeast field since 1962, I missed a comprehensive documentation on this organism, which could help inform students and other researchers interested in this topic.

Writing a textbook is a time-consuming undertaking. How did you start with the book project?

Around the time the yeast sequencing project had been finalized, I started to prepare a set of texts A Short Compendium on Yeast Molecular Biology suitable to be published on a downloadable page on the internet. Fortunately, I kept a collection of papers to document the achievements in various fields of yeast research. I illustrated my compendium with many PowerPoint figures, which my colleagues and I used in presentations. I had adopted this style from ‘BioTutor’, my earlier online collection of Biochemistry in tabular form for medical students.

André Goffeau, the chief coordinator of the Yeast Genome Project, suggested we should assemble a catalogue of outstanding discoveries on how yeast had contributed to Molecular Biology. Finally, it was this suggestion that seduced me into drafting a brochure that gave the full story along with information gathered in my ‘Compendium’. When I offered it to Blackwell Science Publishers, with whom I had had a previous deal, their argument was “… history does not sell …”. However, my French friends insisted that I should not give up. Finally, Wiley-VCH showed an interest in the subject and suggested that I should convert it into a modern textbook since such a book was absent from the market. Thus the first edition appeared in November 2009.

And it was very successful, so now there is the 2nd edition.

You were one of the coordinators of the yeast genome sequencing project. How important was that project for our understanding of eukaryotes in general?

From the beginning, the yeast genome sequencing project was established as aiming at the functional analysis of a whole eukaryotic organism. As I said, even at an early stage of the project, comparisons with other genomes fostered the detection of functions in newly deciphered eukaryotic genomes.

Where do you see the future of yeast research?

Currently, yeast is utilized as a model in Systems Biology. Experiments are underway to generate a fully ‘synthetic’ yeast genome. This allows for its massive restructuring to generate complex genotypes and phenotypic diversity by design, thus opening the door to a new type of broad variation in gene content and copy number. Restructuring of the yeast genome had been suggested earlier, but the techniques available at that time would have only resulted in reducing or minimizing the number of genes.

This field is intimately correlated with the use of yeast as factories in Biotechnology: The scale reaches from valuable pharmaceuticals to various chemical compounds, including biofuels. Modern biotechnology makes use of other yeast species, not just the common Saccharomyces cerevisiae. Currently some 3000 different yeast species are known; they represent a fascinating and extensive world of simple organisms revealing evolutionary relationships as broad as that of the chordates. (Chordates are animals with backbones, including fish, amphibians, reptiles, birds, and mammals). Studies in yeast evolutionary genomics clearly are contributing towards elucidating novel general principles of evolution.

You are a chemist by training. How did you come to yeast research?

When I studied chemistry at Cologne University, Germany, our curriculum did not touch proteins or nucleic acids; biochemistry was a voluntary subject. In 1962, when I had finished my studies, I applied for a post-doctoral position at the newly founded Institute of Genetics in Cologne as I had become fascinated with nucleic acid biochemistry due to a special lecture by the late Fritz Cramer. In the interview, Max Delbrück, the first director of this institute, asked me about my intentions. I answered that “a well-trained chemist should be able to cope with any challenge” – and was accepted.

Thus, I had to learn genetics and molecular biology from scratch. My first job involved the skills of a chemist: synthesizing complex nucleotide compounds, purifying transfer-RNA from tons of brewers’ yeast, and finally participating in the analysis of serine-specific tRNA, all in the laboratory of Hans-Georg Zachau.

In 1967, after moving to the Institute of Physiological Chemistry at Ludwig-Maximilians-University in Munich, Germany, I decided to continue research on tRNA and protein biosynthesis, nota bene, in yeast as the model. Out of this, other themes in yeast research evolved, and I built up my own yeast laboratory.

I have to confess that this little creature never disappointed me. Consequently, after my retirement, I began to summarize my experiences.

What fascinates you most in yeast research?

On the one hand: the simplicity of handling this model system which makes it possible to obtain clear answers to many questions, resulting in a complex picture of cellular life. On the other hand: the continuity with which yeast has maintained its role in Life Sciences research.

How closely related is yeast to humans?

Nobody had expected it, but yeast and humans share about 40 % of highly conserved gene products. Human genes (cDNA), once transferred into yeast, can fully replace the functions of their counterparts.

Several facts underline the importance of yeast research: (i) within the last fifty years, seven Nobel Prize winners (at minimum) have worked with this system; (ii) the yeast genome harbors hundreds of genes that are highly related to ‘disease genes’ in humans: in many cases, the human genes were detected only by comparisons with the yeast genome; and (iii) yeast is successfully used in the research of neurodegenerative diseases, even though yeast has no nervous system whatsoever.

Last but not least, two questions out of curiosity:
As an expert on yeast, are you also an expert in preparing yeast dough?

I don’t like it and, therefore, cannot prepare it.

And another more scientific one:
The CO2 bubbles in drinks with bottle fermentation are famous for being smaller than drinks where CO2 has been added afterwards. Why is that?

This is a question for connoisseurs! I cite two examples, Champagne and Weißbier (cloudy beer). For bottle fermentation, champagne receives the ‘Liqueur de tirage’ containing a little dose of yeast cells. The yeast cells undergo autolysis, improving the alcoholic content and the aroma of the champagne. Also, autolysis generates the fine dispersion of carbon dioxide, which is kept even after ‘reumage’ of the champagne before sale.

(Editor’s note: Reumage or riddling is a process to collect the yeast in the necks of the bottle; for more detail see: Sparkling Wine, Champagne & Co – Part 1; 2) Bottle Fermentation)

Weißbier is brewed from wheat germ in different procedures using ‘top-yeast’. These are yeasts that produce CO2 and have cells which tend to become clustered at the surface in brewing. For the bottle fermentation, small quantities of yeast cells are added, which undergo autolysis and are retained as sediment in the bottle. ‘Kristall-Weißbier’ (popular ‘Champagner-Weißbier’ or filtered cloudy beer) is generated by filtration before it is finally bottled.

Thank you very much for this interview!

Horst FeldmannHorst Feldmann studied Organic Chemistry at Cologne University, Germany, and gained his Ph.D. in this discipline. From 1962–1967 he worked at the Institute of Genetics in Cologne and from 1968–1974 as a lecturer in biochemistry at Munich University, Germany. In 1974 he became Professor of Physiological Chemistry at the Medical Faculty at Munich University, where he remained until his retirement in 1998.

From 1971–2007 Feldmann was one of the organizers of the International “Spetses Summer Schools on Molecular and Cell Biology” and he continues to act as co-organizer and lecturer in various national and international symposia and advanced courses.

His research included sequencing yeast tRNA. He extensively studied tRNA and protein biogenesis, yeast retrotransposons, and mitochondrial genome and was a co-ordinator in the EU project “Sequencing and Analysis of the Yeast Genome”.

  • Webpage of Professor Horst Feldmann
  • H. Feldmann, A Life with Yeast Molecular Biology, in STORIES OF SUCCESS (Eds: V. P. Skulachev and G.Semenzapp) Elsevier, Amsterdam 2008, pp. 275–324.

Selected References

► Louis Pasteur recognized that fermentation is strictly associated with yeast metabolism

  • Études sur la Bière,
    L. Pasteur,
    Gauthier-Villars, Paris, France, 1876.

► Deciphering of the complete genome sequence of yeast

  • Life with 6000 Genes,
    A. Goffeau, B. G. Barrell, H. Bussey, R. W. Davis, B. Dujon, H. Feldmann, F. Galibert, J. D. Hoheisel, C. Jacq, M. Johnston, E. J. Louis, H. W. Mewes, Y. Murakami, P. Philippsen, H. Tettelin, S. G. Oliver,
    Science 1996274(5287), 546–567.
    DOI: 10.1126/science.274.5287.546

► Older textbooks on Yeast genetics, biochemistry, and molecular biology

► Feldmann’s first book on yeast

► More on Max Delbrück, 1st Director of Institute of Genetics, Colone University, Germany

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