초록
<P><B>Abstract</B></P> <P>Geranylgeranyl acetate have been identified as potent and selective inhibitors against <I>Mycobacterium tuberculosis</I>. In this study, the MVA pathway was engineered in <I>Escherichia coli</I> to biosynthesis of the antimycobacterial agent geranylgeranyl acetate from glucose for the first time. Three modules were constructed in <I>E. coli</I> to achieve this objective. AtoB, ERG13 and tHMG1 were overexpressed in the upstream module to accumulate MVA. Then MVA were catalyzed to IPP and DMAPP in the midstream module, which overexpressed Idi, ERG8, MVD1 and ERG12. Finally, in the downstream module, geranylgeranyl acetate were biosynthesized from IPP and DMAPP by overexpressing GGPPS, PgpB and ATF1. The engineered strain DG108 accumulated 57 ± 3.8 mg/L of geranylgeranyl acetate. Further overexpression the Idi, the yield was increased to 119 ± 6.1 mg/L in DG109. The approach described here could be expanded to biosynthesize many antimycobacterial agents and expand the design strategy of metabolic engineering for bioproducts.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Antimycobacterial agent geranylgeranyl acetate was biosynthesized for the first time. </LI> <LI> Alcohol acetyltransferase esterify geranylgeraniol and acetyl-CoA to form geranylgeranyl acetate. </LI> <LI> This novel approach can be expanded to produce many bioproducts. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>