Enzyme cascades and cell factories

Nature’s ability to fuse and tailor simple organic molecules into a vast array of complex chemical scaffolds has fascinated researchers since the early 20th century. The metabolic pathways responsible for this biosynthetic enzymology have provided numerous clinical candidates and lead compounds of immense value as both pharmaceutical and agrochemical agents. Synthetic biology offers a framework through which the purposeful manipulation of biosynthetic pathways and cellular networks can be readily achieved, treating such systems as functional mosaics within which individual enzymatic components may be freely added, removed, modified, or exchanged. This approach offers significant potential for accessing new chemical entities and the construction of optimized ‘cell’ factories for their production.

Projects within this strand of BrisSynBio will build on existing expertise in bioorganic chemistry, molecular enzymology and membrane biophysics to deliver an integrated program of research focused on the isolation, characterization and scalable production of ‘new-to-science’ natural product based therapeutics and agrochemicals. BrisSynBio efforts will be focused on the polyketides, the most structurally and functionally diverse family of bioactive natural products known. These molecules represent challenging, frequently intractable targets for synthetic organic chemistry, and as such biosynthesis offers the only generally applicable route to efficient production.

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