Metabolic engineering of Escherichia coli and Saccharomyces cerevisiae to mutasynthesize natural phenylpropanoids and novel analogs
Chemler, Joseph Anthony
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The current dissertation investigated the biosynthesis of natural and unnatural flavonoids using Escherichia coli and Saccharomyces cerevisiae. Flavonoids are a diverse group of secondary metabolites found ubiquitously in the plant kingdom. Their associated health benefits have gained these fascinating compounds an increasing amount of attention towards their use as medicinal agents, supplements and natural colorants. Reconstruction of biosynthetic pathways in heterologous microorganisms offers significant promise for a scalable means to provide sufficient quantities of desired natural products while using inexpensive renewable resources. Metabolic engineering was utilized to create and enhance flavan-3-ols and isoflavones production platforms in these engineered heterologous hosts. In addition, the enzymatic pathways were fed with synthetic substrates and successful produced flavonoid analogs, some of which possessed high affinity towards human estrogen receptors.