Metabolic Engineering in the Post Genomic Era (Horizon Bioscience)

Rating:
Summary: A heterogeneous collection by various authors
Review: The best place to start reading this book is the last chapter - not the back cover, which says obscurely and uninvitingly that "this book aims to help the reader understand and deal with the plasticity of living cell factories and to turn this plasticity into a desired rather than an adverse direction," and not the first chapter, which is too dense to provide the introduction that the book needs. The final chapter, in contrast, lists a set of fourteen highly pertinent questions that an engineer might ask, starting with "I have now activated the rate-limiting step in the metabolic pathway leading to my product. Why do I not see an increase in production?", and provides short practical answers together with pointers to appropriate chapters where the questions are dealt with in more detail. As there is no Preface, this is the best guide we are likely to get as to why the particular set of authors were collected together to write the book.

There are some excellent chapters, including Stefan Schuster's account of metabolic pathway analysis, which deals with a problem that has become especially acute now that the avalanche of new genomic data has given us a huge amount of sequence information unaccompanied by the enzyme characterization needed for making sense of it all. His own analysis of elementary flux modes provides one way of trying to deduce something about the biochemistry of an organism from the genome alone, without using the (usually missing) kinetic information, but he also mentions alternatives such as extreme pathways (discussed by Bernhard Palsson and colleagues elsewhere in the book).

Other good chapters include accounts of magnetic resonance methods as tools for functional genomics (Kevin Brindle), analysis of regulatory strengths in networks (Pedro Mendes and others), use of databases (Peter Karp), mathematical modelling (Wolfgang Wiechert and Ralf Takors), and so on. Some of these are individually excellent, but it is not easy to see how the whole collection hangs together to make a book, and hence not easy to guess who is likely to buy it.

Incidentally, the answer the editors give to the question that I quoted at the beginning is that it is rare to have a single rate-limiting step in a pathway, and even if there is one control will readily shift to a different enzyme if it is overexpressed. True enough, of course, but I wonder how convincing it is to people who have managed to ignore the message from metabolic control analysis for some three decades. As the experimental evidence (for overexpression of phosphofructokinase in fermenting yeast) has been in the literature now for more than half of that time, it might be better to start with the observation and give the explanation afterwards.