TY - JOUR
T1 - Metabolic engineering of chloroplasts for artemisinic acid biosynthesis and impact on plant growth
AU - Saxena, Bhawna
AU - Subramaniyan, Mayavan
AU - Malhotra, Karan
AU - Bhavesh, Neel Sarovar
AU - Potlakayala, Shobha Devi
AU - Kumar, Shashi
N1 - Funding Information:
We thank the Department of Biotechnology (DBT) and Department of Science and Technology, India, for providing financial support to SK (grants BT/HRD/35/02/09/2008, BT/ PR13028/PID/06/473/2009 and SR/SO/BB-37/2010 respectively). We also like to thank DBT for the grant to NSB for the 500 MHz NMR spectrometers at the ICGEB, New Delhi.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
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U2 - 10.1007/s12038-013-9402-z
DO - 10.1007/s12038-013-9402-z
M3 - Article
C2 - 24499788
AN - SCOPUS:84896040096
SN - 0250-5991
VL - 39
SP - 33
EP - 41
JO - Journal of Biosciences
JF - Journal of Biosciences
IS - 1
ER -