Upload
vhindyreskirayanty
View
239
Download
4
Tags:
Embed Size (px)
DESCRIPTION
farmasi
Citation preview
Starting materials:Amino acids and nucleic acidspseudopelletierinenicotinecaffeineergotmorphinecocaineornithinepurinetyrosinelysinetryptophanAlkaloid Biosynthesis:Nitrogen containing compoundsS. OConnorBiochemistry 7042/5/08ajmalinetryptophan
Endogenous Roles of Natural ProductsinsecticideattractionsignallingUV-protectantsantibiotic/antifungalscentcolorS. OConnorBiochemistry 7042/5/08
Endogenous Roles of Natural Productsalkaloids made by plants
fungi
bacteriaS. OConnorBiochemistry 7042/5/08ergotcocaine
Tetrahydroisoquinoline BiosynthesisS. OConnorBiochemistry 7042/5/08
S. OConnorBiochemistry 7042/5/08How are new genes discovered??Genome Mining (for sequenced prokaryotes/fungi)
Reverse genetics
Homology cloning (P450s, acetyltransferases, terpene synthases)
Large scale sequencingseqeunce all (Taxol)sequence cell type (tabersonine OMe transferase- next page)
Functional expression
6.RNAi screens
S. OConnorBiochemistry 7042/5/08How are new genes discovered??expressed in leaf epidermis
Tetrahydroisoquinoline BiosynthesisS. OConnorBiochemistry 7042/5/08J Nat Prod (2005), 68, 666-673.
How determine the order of the steps in a pathway?
track biosynthetic intermediates before and after knocking out genes
assay enzymes in vitro with different substratesS. OConnorBiochemistry 7042/5/08J Nat Prod (2005), 68, 666-673.
Tetrahydroisoquinoline BiosynthesisTwo oxidative pathsS. OConnorBiochemistry 7042/5/08
Tetrahydroisoquinoline BiosynthesisS. OConnorBiochemistry 7042/5/08
Tetrahydroisoquinoline BiosynthesisS. OConnorBiochemistry 7042/5/08JBC (1995) 270 24475-24481
Tetrahydroisoquinoline BiosynthesisS. OConnorBiochemistry 7042/5/08
Tetrahydroisoquinoline Biosynthesis
STSP450 enzymeS. OConnorBiochemistry 7042/5/08Phytochem 1993 32 79
Tetrahydroisoquinoline BiosynthesisS. OConnorBiochemistry 7042/5/08Tetrahedron Lett 1994 35 3897
S. OConnorBiochemistry 7042/5/08Tetrahydroisoquinoline BiosynthesisTrends in Biotechnology (2005), 23(7), 331-333.
S. OConnorBiochemistry 7042/5/08Tetrahydroisoquinoline Biosynthesis3400 BCjoy plant by Sumerians
1895 Heinrich Dreser working for The Bayer Company
Immunolocalization used to track location of enzymes in morphine biosynthesisS. OConnorBiochemistry 7042/5/08Tetrahydroisoquinoline Biosynthesis
Curr Opin Plant Biol 2005 8 292S. OConnorBiochemistry 7042/5/08Tetrahydroisoquinoline Biosynthesis
Immunolocalization used to track location of enzymes in morphine biosynthesis
S. OConnorBiochemistry 7042/5/08PNAS 2004 101 14091PNAS 2005 102 8495Human Morphine Biosynthesis
we have an opiate receptor
thought to bind peptidesYPFP (Science 1981 212 75)
Caffeinetheobrominexanthosine7-methylxanthosine7-methylxanthineS. OConnorBiochemistry 7042/5/08Caffeine BiosynthesisPurine
Trends Plant Sci. (2001) 6 407.S. OConnorBiochemistry 7042/5/08Caffeine BiosynthesisPurine
Genetically engineered decaf coffee
70% reduction in caffeine content by using RNAi of theobromine synthaseotherwise normal phenotypeNature (2003) 423, 823
Caffeine appears to act as insecticideTrans. Res 2006
Recently discovered natural variant deficient in caffeine synthase Nature (2004) 429, 826.
Promoter of the 3 methyl transferases recently discoveredJ. Biotech. (2005) 119, 20-25.S. OConnorBiochemistry 7042/5/08Caffeine Biosynthesis
EngineeringCaffeinetheobrominexanthosine7-methylxanthosine7-methylxanthine
Ergot Alkaloidstryptophan
S. OConnorBiochemistry 7042/5/08Plant Med 2006
Ergot Alkaloidstryptophan
Mol. Gen. Gen. (1999) 261, 133-141The Alkaloids, G. Cordell pp. 170-218S. OConnorBiochemistry 7042/5/08
Ergot AlkaloidstryptophanS. OConnorBiochemistry 7042/5/08Mol. Gen. Gen. (1999) 261, 133-141The Alkaloids, G. Cordell pp. 170-218
Journal of Biological Chemistry (1995), 270(41), 24475-81. Mol. Gen. Gen. (1999) 261, 133-141The Alkaloids, G. Cordell pp. 170-218Potential for combinatorial biosynthesis?Central amino acid varies
Ergovaline eliminated from a strainof symbiantryegrass staggers(PNAS (2001) 98 12820)S. OConnorBiochemistry 7042/5/08Ergot Alkaloidstryptophan
Mol. Gen. Gen. (1999) 261, 133-141The Alkaloids, G. Cordell pp. 170-218S. OConnorBiochemistry 7042/5/08Ergot Alkaloidstryptophan
S. OConnorBiochemistry 7042/5/08Terpene Indole Alkaloidstryptophan
S. OConnorBiochemistry 7042/5/08Terpene Indole Alkaloidstryptophan
S. OConnorBiochemistry 7042/5/08Terpene Indole Alkaloidstryptophanhere for sarpagine
S. OConnorBiochemistry 7042/5/08Terpene Indole Alkaloidstryptophan