A major reason for the declining prospects of Big Pharma is that synthetic chemistry cannot efficiently access more 'druggable' chemical space (e.g. natural products). Conversely, other alternatives that can access natural product space, such as metabolic engineering, are also restricted. An overwhelming majority of the natural product pathways are uncharacterized, this despite the staggering volume of biological information that is now available. Methodologies that piece together information on genes, enzymes and metabolites from a native producer into a coherent metabolic pathway that can then be engineered into microbial hosts do not exist. We have formulated an algorithm that achieves this exact aim. The algorithm promises to considerably expand the utility of metabolic engineering for synthesizing natural products and their analogues. Moreover, we also propose a high-throughput drug discovery platform that provides unprecedented access to highly-druggable chemical space; conducts faster SAR studies and lead optimization; and, significantly, necessitates no infrastructure substitution.

Systems biotechnology for drug discovery and development

243rd National Meeting (2012)

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