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METABOLIC ENGINEERING OF ALKALOIDS
PRODUCTION IN PLANT
Juan Pan
Department of Plant Pathology
OUTLINE
• alkaloids biosynthesis in plant
• metabolic engineering
• summary
ALKALOIDS
- N-containing small molecule
- Amino acid derivative
- Secondary metabolites
- Defense in plant
- Pharmaceutical uses
Alkaloid biosynthesis
In plant
- monoterpene indole
alkaloid (MIA)
Annu. Rev. Plant Biol. 2008. 59:735-69
MIA biosynthesis scheme
Alkaloid biosynthesis in plant
- benzylisoquinoline alkaloids (BIAs)
dopamine
tyrosine
(S)-norcoclaurine
(S)-reticuline
4-hydroxyphenyl
acetaldehyde
Nature chemical biology, 2009, 5 (5): 292-300
Alkaloid biosynthesis in plant
- tropane alkaloids
Alkaloid biosynthesis in plant
- purine alkaloids
Metabolic engineering of alkaloid biosynthesis
- Overexpressing rate- limiting genes
- Gene silencing to block pathway
- Regulatory element
PMT and H6H overexpression increased scopolamine production
H6H
Proc Natl Acad Sci USA 101: 6786-6791
Silencing COR blocked morphine biosynthetic pathway
COR
dopamine
tyrosine
(S)-norcoclaurine
(S)-reticuline
4-hydroxyphenyl
acetaldehyde
Nat Biotechnol 22: 1559-1566
Nat Biotechnol 22: 1559-1566
Exogenous regulatory factors increased alkaloids production in poppy
Plant Biotechnology Journal (2008) 6, pp. 160–175
SUMMARY
- Overexpression of rate-limiting enzyme for
higher alkaloid production
- Gene silencing to block certain pathway
- Manipulating regulatory elements to increase
alkaloid production
- Combination of several methods