Precursor-directed biosynthesis of epothilone in Escherichia coli.

摘要: Engineered biosynthetic pathways provide a powerful method for generating complex molecules. Precursor-directed biosynthesis, which combines chemical synthesis and enzymatic transformations, allows non-native starting materials to be incorporated into pathways. Using this approach, we achieved the production of anticancer agent epothilone C in Escherichia coli. An E. coli strain was engineered express last three modules pathway (epoD-M6, epoE, epoF) substrate required complement enzymes obtained by synthesis. Under high-density cell culture conditions, processed exogenously fed synthetic at levels comparable native host (1 mg/L) higher than other heterologous hosts. Importantly, precursor-directed approach will allow modifications introduced polyketide backbone may ultimately access analogues with improved pharmacological properties quantities sufficient clinical development.