초록
<P><B>Background</B></P><P>Plasmid expression is a popular method in studies of MVA pathway for isoprenoid production in <I>Escherichia coli</I>. However, heterologous gene expression with plasmid is often not stable and might burden growth of host cells, decreases cell mass and product yield. In this study, MVA pathway was divided into three modules, and two heterologous modules were integrated into the <I>E. coli</I> chromosome. These modules were individually modulated with regulatory parts to optimize efficiency of the pathway in terms of downstream isoprenoid production.</P><P><B>Results</B></P><P>MVA pathway modules <I>Hmg1</I>-<I>erg12</I> operon and <I>mvaS</I>-<I>mvaA</I>-<I>mavD1</I> operon were integrated into <I>E. coli</I> chromosome followed by modulation with promoters with varied strength. Along with activation of <I>atoB</I>, a 26% increase of β-carotene production with no effect on cell growth was obtained. With a combinatory modulation of two key enzymes <I>mvas</I> and <I>Hmg1</I> with degenerate RBS library, β-carotene showed a further increase of 51%.</P><P><B>Conclusions</B></P><P>Our study provides a novel strategy for improving production of a target compound through integration and modulation of heterologous pathways in both transcription and translation level. In addition, a genetically hard-coded chassis with both efficient MEP and MVA pathways for isoprenoid precursor supply was constructed in this work.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s12934-016-0607-3) contains supplementary material, which is available to authorized users.</P>