Abstract
cis-Abienol, a natural diterpene-diol isolated from balsam fir (Abies balsamea), can be employed as precursors for the semi-synthesis of amber compounds, which are sustainable replacement for ambergris and widely used in the fragmented industry. This study combinatorially co-expressed geranyl diphosphate synthase, geranylgeranyl diphosphate synthase, Labda-13-en-8-ol diphosphate synthase and diterpene synthase, with the best combination achieving ~ 0.3 mg/L of cis-abienol. An additional enhancement of cis-abienol production (up to 8.6 mg/L) was achieved by introducing an exogenous mevalonate pathway which was divided into the upper pathway containing acetyl-CoA acetyltransferase/HMG-CoA reductase and HMG-CoA synthase and the lower pathway containing mevalonate kinase, phosphomevalonate kinase, pyrophosphate mevalonate decarboxylase and isopentenyl pyrophosphate isomerase. The genetically modified strain carrying chromosomal copy of low genes of the mevalonate with the trc promoter accumulated cis-abienol up to 9.2 mg/L in shake flask. Finally, cis-abienol titers of ~ 220 mg/L could be achieved directly from glucose using this de novo cis-abienol-producing E. coli in high-cell-density fermentation. This study demonstrates a microbial process to apply the E. coli cell factory in the biosynthesis of cis-abienol.
Highlights
Cis-Abienol, a natural diterpene-diol isolated from balsam fir (Abies balsamea), can be employed as precursors for the semi-synthesis of amber compounds, which are sustainable replacement for ambergris and widely used in the fragmented industry
Microorganisms provide a sustainable and environment-friendly alternative for the production of cis-abienol starting from pure carbon sources and frequently show high product specificity13. cis-Abienol is synthesized from the cyclization of the geranylgeranyl diphosphate (GGPP) which is derived from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) manufactured through either the methylerythritol 4-phosphate (MEP) pathway in prokaryotes or the mevalonate (MVA) pathway in archaea/eukaryotes[14,15,16]
In the previous s tudy[28], it has proved feasible that overexpressing the Lpps gene and sclareol synthase gene along with the native MEP pathway to produce sclareol in E. coli
Summary
Cis-Abienol, a natural diterpene-diol isolated from balsam fir (Abies balsamea), can be employed as precursors for the semi-synthesis of amber compounds, which are sustainable replacement for ambergris and widely used in the fragmented industry. A sufficient supply of IPP and DMAPP is essential This has been often achieved by the expression of the idi and dxs (1-deoxy-d-xylulose 5-phosphate reductoisomerase) gene in the MEP pathway[24]. In this study, based on our previous w ork[27,28], cis-abienol was produced by assembling a biosynthetic pathway in an engineering E. coli, using the heterologous MVA pathway combined with the additional of CrtE gene, Labda-13-en-8-ol diphosphate synthase (LPPS) gene from Salvia. This study has begun the necessary foundations for a more sustainable route of cis-abienol production
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