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