Fermentation products are indigenous to many civilizations, and they have been produced by industriessince a long time. Saccharomyces cerevisiae S288C (commonly known as baker's yeast) is the strain mainly usedin the Glucose based fermentation industries. We have seen the use of same yeast strain at different places withdifferent Phenotypic Constraints. The way to improve the adaptability of considered strain for desired phenotypicconditions, using smart selection of genes through cybernetic modeling is illustrated. Phylogenetic homologues forall S. cerevisiae S288c Glucose Fermentation pathway genes were screened to search evolutionarily relatedfunctional domains in other yeast strains like Saccharomyces cerevisiae YJM789, Candida glabrata CBS138,Kluyveromyces lactis NRRL Y-1140, Ashbya gossypii ATCC10895 etc., which are adapted naturally in different setof environment. We observed that Saccharomyces cerevisiae YJM789, Candida glabrata CBS138, Ashbyagossypii ATCC10895, Kluyveromyces lactis NRRL Y-1140 possess highly conserved functional domains, whichcan be carefully selected based on usage. This study aims at designing an algorithm to select and incorporateevolutionary homologues for genes of a considered strain, which mostly show sub-optimal performance in thedesired set of experimental constraints. Such a consideration of native microenvironment and evolutionarycloseness in the selection of functional homologues of the entire genetic set can thus be significantly fruitful.