Protein EngineeringHandbookEdited by Stefan Lutz and Uwe T.Bornscheuer.

Wiley-VCH, Weinheim 2009, 1015 pp. (2 vols),hardcover E 349.00.—ISBN 978-3-527-31850-6

The Protein Engi-neering Handbookprovides the firstcomprehensiveoverview of thehighly cross-disci-plinary field ofprotein engineer-ing that many re-searchers and stu-dents have beeneagerly awaiting. Being complementaryto recently published handbooks thatfocus on specific applications or meth-ods for the integration of non-naturalamino acids, chemical peptide synthesisand in vitro translation, the 37 chaptersprovide insight into the foundations forthe choice of ideal starting points forenzyme engineering, some importantanalytical tools and some of the mostimportant concepts and tools forenzyme engineering, selection andscreening. Some chapters also includedetailed experimental protocols.

After a first wave, where protein struc-tures started to become broadly avail-able and where new tools in molecularbiology, including the invention of theTaq polymerase and PCR, enabled thesimple manipulation of nucleotide andprotein sequences, we now face thetime of computational modelling of pro-tein structures, structure-guided rede-sign of proteins. The powerful laboratoryevolution of proteins has become stan-dard in many labs. Engineered biophar-maceuticals (e.g. , insulin) are on themarket, and industrial enzymes, engi-neered by rational redesign and by di-

rected evolution, are used on an indus-trial scale. Nowadays protein engineeringis also employed in basic research tofacilitate studies about protein folding,protein stability, enzymatic mechanisms,protein structures and dynamics, for pro-tein solubilisation and purification, pro-tein interactions (focus of Volume 1, e.g. ,Chapters 1–8, 13, 14) and, at the sametime, to create useful catalysts, biosen-sors, peptides and biomaterials for in-dustrial and medical applications (exam-ples mainly in Volume 2). I do not knowany other book that summarises and in-cludes all these fascinating new aspectsin protein engineering. Although fo-cused on enzyme engineering, somechapters also provide an overview of theconcepts and methods used for the en-gineering of antibodies and other thera-peutic proteins. Some highly interestingchapters at the end of Volume 2 give animpression about protein engineeringfor the design and production of newbiomaterials for new industrial and medi-cal applications.

Chapter 1 reminds us about the fun-damentals in biochemical analyses,which are essential for the design of theperfect screening assay and analysis ofnew enzyme variants. The next chaptersdiscuss how promiscuity can be used tochoose a promising starting point forenzyme engineering and promising con-cepts and structural regions of enzymesfor improving their selectivity. The gener-al layout of the individual chapters withthe outlook and conclusions for proteinengineering helps to find the link to pro-tein engineering also in the more com-plex topic of protein folding and dynam-ics. Moreover the outlook to new univer-sal selection systems in Chapter 13,which provides detailed protocols forthe generation of expression libraries,provides an interesting additional view.

Several topics that, at first sight, seemto be repetitive complement each otherdue to their specific focus on more theo-

retical or practical aspects. While Chap-ters 8 (focused on three major proteincores) and 12 provide insight into appli-cations towards the de novo design ofnew functions and designed enzymesthat mimic the selectivity, efficiency andregulation of natural proteins, Chapter 9gives a broad overview of the state ofthe art of technologies from the startingpoint of discovery from nature up totechnologies for mutagenesis andscreening, and even includes experimen-tal details. Most other specific methodsfor protein engineering are found inVolume 2. However, from the point ofproviding a compact overview, somespecific topics and chapters could havebeen fused into single chapters, like thevery special intein technologies (Chap-ters 10 and 15 or Chapters 9 and 11).Speculations about possible photoactiva-tion of enzymes or pharmaceuticals byusing intein technologies sound up-and-coming. Compared to other more gener-al chapters, I also did not see essentialadditional information in the very specialChapter 17 about engineering a lipasefor altered enantioselectivity.

In most chapters, especially in Volume2, well-chosen figures visualise the infor-mation of the text and facilitate readingand understanding of the huge diversityof methods and applications of proteinengineering. Unfortunately, Chapter 31describes the interesting field of engi-neered cofactor specificities mainly by asummary of selected examples from lit-erature. Pointing out common principlesand strategies would have been helpful.However, similar to other specialisedtopics, like cyanophycin synthetases (33)and biosynthetic pathway engineering(34), the strong impact of enzyme engi-neering in a vast diversity of applicationsis depicted. Chapter 20 describes theSCHEMA algorithm, providing an excel-lent demonstration of the gaining impor-tance of bio-computational tools andstrategies for protein engineering.

One by One

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A series of chapters (24–30) gives anice overview of highly important specif-ic and also broadly applicable screeningassays, reaching up to new FACS tech-nologies. Also the expression technolo-gies linking the generation of gene di-versity with screening and functionalanalysis of protein variants are well pre-sented and include smart new in vivo se-lection systems (Chapter 23). The chap-ters dealing with expression and displaytechnologies provide at least some indi-cations about relevant applications ofprotein engineering for therapeutic pro-tein development in addition to thefocus of the handbook in enzyme engi-neering. Due to the importance of pro-tein stability for all kinds of applications,from industrial biocatalysis up to phar-maceutical applications, I am somehowmissing a chapter dedicated to generalconcepts and methods for protein stabi-lisation. However, fulfilling all wisheswould probably quickly fill a thirdvolume.

Although the authors of Chapter 1 seethe basic goal in protein engineering tobe the creation of altered enzyme cata-lysts, the two volumes of this handbookprovide a much broader view. The edi-tors do not claim to provide an all-inclu-sive, up-to-date collection of knowledgeand methods, but a review of today’sbasics and an introduction to selected,new, promising strategies, as well as in-spiration for the experienced protein en-gineer. In this respect, the two volumesfully achieve these goals and live up tomy expectations, being useful and com-prehensive for a broad readership fromstudents to experienced protein engi-neers.

Anton GliederGraz University of Technology (Austria)DOI: 10.1002/cbic.200900410

Single Cell Analysis:Technologies and ApplicationsEdited by Dario Anselmetti.

Wiley-VCH, Weinheim 2009, 284 pp., hard-cover E 89.90.—ISBN 978-3-527-31864-3

The book SingleCell Analysis,edited by DarioAnselmetti, pro-poses introducingthe reader to thevast and hetero-geneous field ofthe same name,also linking it toso-called “Systemsnanobiology”, al-though the analogy between the twodisciplines is not entirely obvious. It be-comes a bit clearer when looking at thecontents of the different chapters, whereultrasensitive methods with single-mole-cule sensitivity are very prominently rep-resented.

The most important aspect of cellanalysis nowadays is certainly imaging;for this reason, the first section, contain-ing three chapters, is devoted to thistopic. First, fluorescence imaging ofsingle molecules is demonstrated on nu-clear splicing factors. Second, the imag-ing of cell surfaces by atomic force mi-croscopy is described, putting bacterialS-layers into focus. The third chapter,ACHTUNGTRENNUNGactually one of the best of the book, isdevoted to electron tomography to elu-cidate cellular ultrastructure.

In the next section of the book, “Tech-nologies”, five chapters are grouped to-gether that actually share no obviouscommon theme, but could be under-stood somehow as an “information pro-duction line” of relevant molecules andtheir properties. Microfluidic approaches,as first outlined in the fourth chapter“Single Cell Proteomics”, are discussed inaltogether three chapters (4, 5, 7), al-though one would have probably beensufficient, especially since none of thechapters actually bothers to give aACHTUNGTRENNUNGdetailed outline of modern microfluidicstechnology in general. Chapter 6, forsome unclear reason placed betweenthe microfluidics chapters, gives a verybrief glimpse, not more, of single-cell

mass spectrometry. Chapter 8, interest-ing but technically rather specialized,discusses the possibility of measuringthe mechanical features of single cells byoptical stretchers.

The third section of the book, labelled“Applications” is again less structuredthan the previous one, ranging fromsingle-cell immunology studies (9) viatumour cell characterization mainly byflow cytometry (10), and a chapter called“Cell Heterogeneity” that could (al-though it is not) be something like theintroduction to the previous two, to“Genome and Transcriptome Analysis ofSingle Tumour Cells” (12). There is anoverall redundancy apparent in the titlesof these chapters.

All in all, this book unfortunately doesnot really help in making the field as awhole more structured or comprehensi-ble. In its main body, it is mainly a selec-tion of what can nowadays be donewith various techniques on the single-cell level. There is no obvious threadthrough it. The overall structure, “Imag-ing”, “Technologies”, “Applications” doesnot help much in organizing the con-tent, because imaging is a technology,and nearly all the chapters are dominat-ed by specific applications, rather thanproviding a broad overview. Only twochapters, 3 and 4, represent book chap-ters in the strict sense, all the others aremore or less excerpts of previously pub-lished research articles, with little to nopropaedeutic quality.

Although I have much appreciationfor the scientific contents of the book, Iam missing clear cross-links between thedifferent chapters. Many chapters pro-vide detailed “materials and methods”sections, which are not really beneficialin a textbook that is not meant to be auser manual, and should be omitted.

Taken together, this selection ofsingle-cell technologies and applicationsmay be interesting to get a first glimpseof a vast field, but it is no true comple-ment to reading an arbitrary selection ofresearch or overview articles.

Petra SchwilleTechnische Universit�t Dresden(Germany)DOI: 10.1002/cbic.200900427

2112 � 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ChemBioChem 2009, 10, 2111 – 2114