Chemical Complementation

Baker, K., Bleczinski, C., Lin, H. et al. (2002) Chemical complementation a reaction-independent genetic assay for enzyme catalysis. Proceedings of the National Academy of Sciences of the United States of America, 99, 16537-16542. 

Baker K, Bleczinski C, Lin H, Salazar-Jimenez G, Sengupta D, Krane S, Cornish VW. Chemical complementation a reaction-independent genetic assay for enzyme catalysis. Proc. Natl. Acad. Sci. U.S.A. 2002 99 16537-16542. 

Libraries of synthetic combinatorial chemicals complement libraries of natural product metabolites, but do not duplicate or replace them. Examples of side-by-side screening of synthetic combinatorial chemicals and microbial fermentation extracts indicate that both sets of chemical diversity can provide unique leads. The quantity of leads generated by each method is irrelevant, if the quality of the lead is not considered. Therefore, scientific research should be focussed not on which type of library is better, but rather how to take advantage of both resources in a cost-effective and timely manner. 

The general, incompatible-element depleted nature of the majority of MOREs and their sources is well explained by the extraction of the continental crust. Nevertheless, the bulk continental crust and the bulk of the MORE sources are not exact chemical complements. Rather, the residual mantle has undergone additional differentiation, most likely involving the generation of OlEs and their subducted equivalents. In addition, there may be more subtle differentiation processes involving smaller-scale melt migration occurring in the upper mantle (Donnelly et al., 2003). It is these additional differentiation processes that have... 

A fourth possibility, that ultramafic cumulates representing the chemical complement to the andesitic cmst are present in the uppermost mantle, is not supported by studies of peridotite xenoliths, which show a predominance of restitic peridotite over cumulates (e.g., WUshire et al., 1988). If such cumulates were originally there. 

All of the above processes require return of mafic to ultramafic lithologies to the convecting mantle. These lithologies are the chemical complement of the present-day andesitic crust. Thus crustal recycling, in various forms, must have been important throughout Earth history. 

Chemical Complementation Bringing the Power of Genetics to Chemistry... 

Fig. 4.1-1 Chemical Complementation combines the power of genetic assays and small molecule chemistry to understand small molecule function and develop new chemistry inside the cell.

As intended, no further modifications to Chemical Complementation were needed to extend this assay to detect glycosynthase activity. All that was required to detect glycosynthase activity was to add the Dex and Mtx saccharide substrates. This result shows the generality of Chemical Complementation, and the ease with which it can be applied to new chemical reactions. Moreover, it shows that Chemical Complementation can detect not only bond cleavage but also bond formation reactions. Although, the size of the Glul97 saturation library selected here was quite small, with only 32 members at the DNA level, the transformation efficiency of S. cerevisiae, however, allows much larger libraries, in the order of 105-107. 

The genetically complemented mutant ao+msas restored the biosynthesis of all the missing metabolites. Chemical complementation, performed by independent incorporation of 6-MSA, diepoxide 142, and aspyrone 138 to separate growing cultures of aoAmsas mutants, revealed that these compounds produced similar effects and restored the biosynthesis of both 139 and 139. ... 

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