FEMS Yeast Research

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Book Review

Yeast Intermediary Metabolism
Jens Nielsen, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

Saccharomyces cerevisiae, or often just referred to as yeast, is widely used both in industry and in research laboratories. It has been used for centuries in the production of beer, bread and wine, and in the biotech industry it is used for the production of biofuels (ethanol and farnesene), pharmaceutical ingredients (artemisinic acid), nutraceutical ingredients (resveratrol), pharmaceutical proteins (insulin and other hormones), and vaccines (hepatitis and HPV). In research laboratories yeast is used as a model organism for studying eukaryal molecular biology and biochemistry. A number of pathways are conserved between yeast and human cells so new insights into the function of these pathways can be obtained through studies of yeast, which can make the studies faster and cheaper.

Metabolism can be seen as the core of cellular functions as it provides ATP, co-factors and building blocks required for cell growth and proliferation. Furthermore, in connection with development of novel yeast cell factories for production of fuels and chemicals it is essential to have a deep understanding of yeast metabolism. The wonderful book “Yeast Intermediary Metabolism” by Dan G. Fraenkel is therefore timely and it represents a valuable contribution. The book will be important for graduate students and post docs that are studying yeast physiology and metabolism, but it may also serve as a textbook for advanced courses in metabolism. The book gives a very comprehensive overview of yeast metabolism, and it is well illustrated with figures that provide pathway maps. A particular strong feature is the elaborate linking of specific enzymatic reactions and genes, which is the basis for building so-called genome scale metabolic models (several such models have been reconstructed for yeast), but also something that is of great value for metabolic engineering.

The book contains 11 chapters. The first chapter provides an overview of metabolism and its context. This includes a brief description of the nutritional requirements of yeast, cell biology and cellular composition in terms of macromolecules and metabolites. The second chapter gives a summary of enzymes and co-enzymes, including a brief description of enzyme classification and their kinetics. Chapter three gives an overview of the transport of small molecules. Here different modes of transport are described and the chapter is a good introduction to molecular transport. There is relatively little yeast specific information, but this is partly due to the fact that transport is one of the “dark” areas of metabolism in general. Thereafter follows three chapters on central metabolism, i.e. the production of Gibbs free energy in the form of ATP, redox power in the form of NADH and NADPH, and precursor metabolites. Glycolysis, which has been extensively studied in yeast, is of course described in details, but also other pathways are very well covered, i.e. the TCA cycle, pentose-phosphate metabolism and respiration. Considering the importance of hexose transport, one could, however, have wished for a little more detail, e.g. classification of the HXT genes into high and low affinity transporters. Another issue that is not covered in detail is how acetyl-CoA metabolism is distributed between different cellular compartments, which is quite important as it represents an important branch point between energy and biosynthetic metabolism. Naturally following central metabolism comes three chapters on biosynthesis. Besides covering pathways to amino acids, nucleotides and lipids (a whole separate chapter is devoted to lipid biosynthesis), there is a very detailed description on the biosynthesis of different co-factors. This is really enjoyable to read, and I cannot think of any other resource covering this part of metabolism in such great detail. The only thing one could wish for would be little more information on the use of these different co-factors, e.g. what is the role of lipoyl proteins. Of course, in covering many aspects of a broad field like metabolism one expects that certain parts are missing, in this case direct sulfurylation pathway for cysteine biosynthesis and ER-associated lipid biosynthesis are not mentioned. However, this is really just a minor criticism as I think Fraenkel found a very good balance between covering all parts of metabolism without getting lost in the details. The last two chapters of the book cover more catabolism, i.e. catabolism of other sugars, lipids, amino acids etc., and stress. The chapter on stress gives a good overview of some key pathways involved in stress, and it is actually the only part of the book where issues on signaling and regulation are covered. The lack of regulation and signaling is in particular of importance for glucose metabolism where glucose repression on the Crabtree effect could have been covered in more depth in the last chapter (figure 11-1 covering this topic is over-simplified). On the other hand, considering the complexity of regulation and the fact that many regulatory pathways have not been fully elucidated I do, however, understand the decision to not cover this topic in detail.

Despite these few issues, I find this a very enjoyable book to read. It is very rich with factual information and I will for sure use it extensively in future discussions on yeast metabolism, and I will strongly encourage all my graduate students and post docs working on yeast metabolic engineering to study this book in detail.

Dan G. Fraenkel (2011) Yeast Intermediary Metabolism, Cold Spring Harbor Laboratory Press, New York