Metabolic engineering of chloroplasts for artemisinic acid biosynthesis and impact on plant growth

Journal of biosciences

Karan Malhotra¹  Shobha Devi Potlakayala²  Bhawna Saxena¹  Mayavan Subramaniyan¹  Neel Sarovar Bhavesh¹  Shashi Kumar1¹ 

[1] International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India$$;School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA$$

关键词: Antimalarial drug;    artemisinin;    gene pyramiding;    isopentenyl-diphosphate/isopentenyl pyrophosphate (IPP);    metabolic flux;    mevalonate (MEV) pathway;    plastome;    transplastomics;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

Chloroplasts offer high-level transgene expression and transgene containment due to maternal inheritance, and are ideal hosts for biopharmaceutical biosynthesis via multigene engineering. To exploit these advantages, we have expressed 12 enzymes in chloroplasts for the biosynthesis of artemisinic acid (precursor of artemisinin, antimalarial drug) in an alternative plant system. Integration of transgenes into the tobacco chloroplast genome via homologous recombination was confirmed by molecular analysis, and biosynthesis of artemisinic acid in plant leaf tissues was detected with the help of 13C NMR and ESI-mass spectrometry. The excess metabolic flux of isopentenyl pyrophosphate generated by an engineered mevalonate pathway was diverted for the biosynthesis of artemisinic acid. However, expression of megatransgenes impacted the growth of the transplastomic plantlets. By combining two exogenous pathways, artemisinic acid was produced in transplastomic plants, which can be improved further using better metabolic engineering strategies for commercially viable yield of desirable isoprenoid products.

【 授权许可】

Unknown