Generating Complex Biological Traits through Combinatorial and Multigenome Expansion of the Sampling Space

There are many complex phenotypes/strains that are desirable for practical applications in the context of Cell or Metabolic Engineering. One example is when one desires to endow a platform organism with a biosynthetic or catabolic pathway that another organism may possess. Such a pathway may involve several enzyme-coding genes as well as regulatory genes, but these genes may be unknown. Another example is the ability to endow a platform organism with unusual membrane structures or a stress-response system that some other organism possess, or by re-engineering a native stress response system. This would be important in bioprocessing and advanced bioremediation applications. Endowing cells with such desirable capabilities requires several or many genes deriving from other organisms, including genes from targeted metagenomic libraries. Whether sampling a single-genome space or a multi-genome space, a key difficulty that must be overcome is the ability to sample the combinatorial space of genetic-loci interactions that are necessary for developing the synthetic or semi-synthetic phenotype. How does one attack this class of problems in the context of synthetic biology and cell engineering?