Biosynthetic Polypeptide Libraries

Manipulation of the biosynthetic pathways leading to natural compounds, so-called combinatorial biosynthesis, is presented in the third section, with particular attention paid to the opportunities arising from polyketide biosynthesis. Finally, combinatorial biotransformation of natural or synthetic compounds by means of isolated enzymes or whole microorganisms is presented in the fourth section. 

Although many factors are involved in the evolution of an organism, its life-cycle plays an important part regulating the pace of evolution and can be compared to the chemical synthesis of a library. Higher organisms evolve very slowly and can be compared to classical, information-rich low-throughput chemistry methods to prepare 

Both gram-negative and, more recently, gram-positive bacteria (1,16,17) have been used to display various peptide libraries that were screened to find ligands (18-20), antibodies (21,22), and vaccines (23). Surface display on yeasts has produced the very popular yeast-two hybrid system and some of its variants several recent papers and reviews are referenced here (24-27). These methods have been used to prepare and select polypeptides and proteins for various applications, including the identification of binding partners in protein-protein interactions where this is the technique of choice (28-31). 

An intriguing comparison can be made between phage display libraries and synthetic SP, pool pol5q)eptide libraries  

Multiple copies of each library individual are easily obtained by controlling the library production steps (mix-and-split synthesis versus DNA recombination and amplification of phage populations). 

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Shusta, E. V., VanAntwerp, J., and Wittrup, K D. (199b). Biosynthetic polypeptide libraries. Curr. Opin. Biotechnol. 10, 117-122. 

K. D. Wittrup. Biosynthetic polypeptide libraries. Curr Opin Biotechnol (1999) 10(2) 117-22. 

BIOSYNTHETIC POLYPEPTIDE LIBRARIES copy 1 I gene 1 gene k gene d ]. gene n ... 

BIOSYNTHETIC POLYPEPTIDE LIBRARIES 517 INTEGRIN-BINDING MOTIFS... 

Biosynthetic polypeptide libraries are the translation of a genetic, oUgonucleotide-based diversity information into a biologically relevant pool of p)otential binders, catalysts, or receptors. The previous section illustrated how the availability of complex DNA sequences and of the appropriate techniques for their synthesis and manipulation allows the biological production of diverse polypeptide libraries. However, the intrinsic properties of nucleotide sequences have themselves stimulated researchers into budding a variety of oligonucleotide (ON) libraries per se for a variety of applications. 

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