De novo biosynthesis of antimycobacterial agent geranylgeranyl acetate from glucose

Abstract

Geranylgeranyl acetate have been identified as potent and selective inhibitors against Mycobacterium tuberculosis. In this study, the MVA pathway was engineered in Escherichia coli to biosynthesis of the antimycobacterial agent geranylgeranyl acetate from glucose for the first time. Three modules were constructed in E. coli 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.