Heterologous biosynthesis of costunolide in Escherichia coli and yield improvement

Costunolide, the main bioactive compound of the medicinal plant, Radix Aucklandiae , is a sesquiterpene lactone (SL) and has a broad range of biological activities. It is also a precursor of many biologically-active SLs and is a branching point in the biosynthesis of SLs. Here we have reconstituted the costunolide biosynthetic pathway in Escherichia coli by co-expression of three genes ( GAS , GAO , LsCOS ) involved in costunolide biosynthesis and eight genes involved in converting acetyl-CoA into farnesyl diphosphate from mevalonate pathway. Costunolide production was then detected. By screening and optimization of cultured medium and inducing temperature, costunolide yield was up to 100 mg l −1 in E. coli .