ComGene
Combinatorial Genetics Platform
ComGeneä
is a combinatorial genetics based lead compound molecular diversity
engine. The
biocatalytic production of small molecules typically involves the
concerted activities of several enzymes – a biosynthetic enzyme array
(BEA). It
is known that the substitution of one or more similar enzymes into a given
BEA can result in the production of novel compounds (including novel
backbone), often with novel pharmacologic activities. Thus, the potential of this generalized approach for drug discovery
is tremendous.
However, until the development of ComGeneä,
a high-throughput platform for exploiting this strategy and realizing its
potential did not exist.
ComGeneä
facilitates the rapid substitution of genes and enzymes into biosynthetic
enzyme arrays, resulting in a complete combinatorial array of
virtually any matrix dimension. The result is the generation of unique molecular libraries and
provides for the production of novel structural chemotypes.
As a result, ComGeneä
is much more efficient than conventional single gene swapping, gene knock
out, and in vitro reconstitution approaches. ComGeneä
also requires no a priori knowledge of the enzymes or genes of the
BEAs to be interchanged, absolute requirements of all conventional
approaches.