Amino Acids - MIT OpenCourseWare Amino acids and nucleic acids NMe HN O OH H H N N N N O O CH3 CH3 H3C

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Text of Amino Acids - MIT OpenCourseWare Amino acids and nucleic acids NMe HN O OH H H N N N N O O CH3 CH3...

  • Amino Acids: Ornithine Lysine Tyrosine Tryptophan

    Purine

    Starting materials: Amino acids and nucleic acids

    NMe

    HN

    OHO

    H

    H

    N

    N N

    N

    O

    O

    CH3

    CH3

    H3C

    N Me O

    CO2Me

    O

    pseudopelletierine

    nicotine N

    N MeH

    caffeine

    ergot

    O

    NCH3

    HO

    HO

    HH

    morphine

    CO2

    NH3

    OH

    N H

    NH3

    CO2

    N

    NN

    N

    NH2

    O

    OHOH

    OP-O

    O-

    O

    NH3

    CO2

    H3N

    CO2

    H3N

    NH3 N

    Me O

    cocaine

    ornithine

    purine

    tyrosine

    lysine

    tryptophan

    5.451 F2005 Alkaloid Biosynthesis: Nitrogen containing compounds

    (fungus)

    rebeccamycin staurosporine

  • 5.451 F2005 Alkaloid Biosynthesis: Purine Derived Products: Caffeine

    T

    Figure removed due to copyright reasons. Please see Figure 4 in Trends Plant Sci 6 (2001): 407.

  • 5.451 F2005 Alkaloid Biosynthesis: Purine Derived Products: Caffeine

    Genetically engineered decaf coffee

    70% reduction in caffeine content by using RNAi of theobromine synthase

    otherwise normal phenotype

    Nature (2003) 423, 823

    Recently discovered natural variant deficient in caffeine synthase

    Nature (2004) 429, 826.

    Promoter of the 3 methyl transferases recently discovered

    J. Biotech. (2005) 119, 20-25.

  • pyrrolizidine

    5.451 F2005 Alkaloid Biosynthesis: Ornithine and Lysine Derived Products

    N

    H

    homospermidine (via 2 putrescines)

    tropanes

    N Me

    nicotine N

    N MeH

    quinolizidines

    N

    indolizidines

    N

    NH2 H2N

    putrescine (via ornithine) 2 acetates

    NH2 H2N

    putrescine (via ornithine) nicotinic acid

    N Me

    pseudopelletierine

    cadaverine (via lysine) 2 acetates

    2 cadaverines pipecolic acid (via lysine) 1 acetate

  • pyrrolidines nicotine

    N

    N MeHN

    H

    5.451 F2005 Alkaloid Biosynthesis: Ornithine Derived Products

    N

    CO2H

    N

    OH

    O

    N H N

    H

    H

    N MeH

    N MeH

    N Me

    H-

    H+

    H+

    NADP+

    CO2

    nicotinic acid

    B3 (niacin)

  • pyrrolizidine

    5.451 F2005 Alkaloid Biosynthesis: Ornithine Derived Products

    N

    H

  • pyrrolizidine

    5.451 F2005 Alkaloid Biosynthesis: Ornithine Derived Products

    N

    H

    PNAS (1999) 96, p. 14779

    Origin of a secondary metabolic pathway? Found only in angiosperms

    N H

    H2N NH2

    H2N NH2N H

    H2N NH2+

    NH2 E

    N H

    H2N NH2+

    H N

    E NH2

    E = elF5A

    H N

    E NH2

    OH

    hypusine

    deoxyhypusine

    spermidine

    lysine of transcription factor

    putrescine homosperrmidine

    HS synthase

    DH synthase

    deoxyhypusine synthase

  • piperidines ornithine

    5.451 F2005 Alkaloid Biosynthesis: Lysine Derived Products

    N H

    H3N CO2

    NH2

    H3N CO2

    NH2

    lysine

  • quinolizidines

    5.451 F2005 Alkaloid Biosynthesis: Lysine Derived Products

    N

    N

    H2N NH2 H2N CHO NH NH

    NH

    N H

    HNH

    CHO H

    NH2

    NH

    CHO H

    CHO

    CHO H

    NH2 H2N

    N H

    H2N

    N

    NH2 H2N NH2

    N H

    OHC NH2 OHC

    N

    H CHO

    N

    H2N

  • indolizidines

    5.451 F2005 Alkaloid Biosynthesis: Lysine Derived Products

    N

    H3N NH2 NH N

    CO2

    H2N H

    CO2 O

    CO2H

    NH

    O O

    SCoA H H O

    O

    O

    OH O

    MeOO

    O

    N

    HO

    MeO

    O O

    OH H

    OMe

    pipecolic acid acetate

    polyketide/peptide rapamycin

    cyclohexyl CoA

    shikimic acid

  • 5.451 F2005 Alkaloid Biosynthesis: Ornithine Derived Products

    Source of alkaloids arthropod eats plant; or ant or symbiontof ant makes alkaloid vertebrate (frog) eats ant

    after injestion, can be derivatized by frog to make more poisonous See Figure 1 in PNAS 100 (2003): 11092.

    alkaloids found in ants and frogs See Figure 1 in PNAS 101 (2004): 8045.

    Figure removed due to copyright reasons.

    Figure removed due to copyright reasons.

  • 5.451 F2005 Alkaloid Biosynthesis: Ornithine Derived Products Chemical Defense

    Figures removed due to copyright reasons.

  • 5.451 F2005 Alkaloid Biosynthesis: Ornithine Derived Products

    Removed due to copyright reasons.

  • pyrrolizidine

    5.451 F2005 Alkaloid Biosynthesis: Ornithine Derived Products Outwitting the Chemical Defense- Detoxification by oxidation

    N

    H

    N

    H CHO

    O

    detoxification

    Figure removed due to copyright reasons. Please see Figure 1 in PNAS 99 (2002): 6085.