天然药物化学第二讲课件

Introduction to the Studies of Biosynthesis of Natural Products,Yuemao Shen yshensdu.edu.cn,College of Pharmaceutical Sciences, Shandong University September 13, 2010,3. Three examples,The Biosynthesis of Taxol,Techniques we applied: A. Stable isotope labeling, feeding B. Radioactive isotope tracing in Enzymatic acetylation Conclusion: 10-deacetylbaccatin-III is a precursor of taxol,Hypothetic multiple pathways towards taxol,The biosynthesis of rifamycin B,Two possible pathways, A and B, towards rifamycin B. A demanded that protorifamycin I is the key intermediate and the oxygen at the C-8 position is introduced later. B required that the oxygen at C-8 is of the same origin as the carbon of C-8, i.e., from the carboxyl group of AHBA.,Methods and Techiques: DNA mutagensis; stable isotope labeling, feeding; 13C NMR assay; LC-ESI-MS Conclusions: A. The C-8 oxygen is the same origin as the C-8 carbon B. The formation of naphthoquinone precedes the lactamization C. The biosynthesis of type I polyketides occurs progressively,The sequence of the formation of the naphthoquinone and lactam,The biosynthesis of Streptomyces spore pigment,Origins of Building Blocks,Common Building Blocks,C1,C2,C5,Common Building Blocks,C6C3,C6C2,C6C1,C6C2N,Common Building Blocks,C4N,C5N,Indole-C2N,Common FAs,Acyl Thioester,General Chemistry,Aldol and Claisen Condensation,Aldol and Claisen Condensation,Aldol and Claisen Condensation,Malonyl CoA: activated acetyl CoA,Malonyl CoA: activated acetyl CoA,Overall Biosynthetic Scheme,Bacterial Aromatic Polyketides,Bacterial Aromatic Polyketides,Bacterial Aromatic Polyketides,Bacterial Reduced Polyketides,A, Acetate; P, Propionate; B, Butyrate; G, Glycerol; S, Starter from branched chain or cyclic units,Bacterial Reduced Polyketides,Bacterial Reduced Polyketides,Fungal Aromatic Polyketides (Non-reduced/Partially Reduced Polyketides),Orsellinic acid,Tetrahydroxynaphthalene (THN),6-Methylsalicylic acid (MSA),Norsolorinic acid,Fungal Aromatic Polyketides with unusual features - mixed reduced/non-reduced,Unusual acetate label Unusual starter Unusual mix,Fungal Highly Reduced Polyketides,T-toxin,Mevacor,Statins,hydroxy-methylglutaryl-CoA (HMG-CoA).,Fungal Aromatic Polyketides (Non-reduced/Partially Reduced Polyketides),Orsellinic acid,Tetrahydroxynaphthalene (THN),6-Methylsalicylic acid (MSA),Norsolorinic acid,Plant Polyketides (Bacterial polyketides made by the same type of PKS),chalcone in higher plants,1,3,6,8-tetrahydroxynaphthalene (THN) in Streptomyces griseus and S. coelicolor,3,5-dihydroxyphenylacetic acid (DHPA) in Amycolatopsis mediterranei and A. orientalis,Plant Polyketides (Starter: Phenylpropanhoid Pathway),chalcone,Plant Polyketides (Bacterial polyketides made by the same type of PKS),chalcone in higher plants,1,3,6,8-tetrahydroxynaphthalene (THN) in Streptomyces griseus and S. coelicolor,3,5-dihydroxyphenylacetic acid (DHPA) in Amycolatopsis mediterranei and A. orientalis,Nonribosomal Peptides,Antibiotics,Nonribosomal Peptides,Antibiotics,Nonribosomal Peptides,Immunosuppresants,Nonribosomal Peptides,Toxins,Nonribosomal Peptides,Nonribosomal Peptides,Nonribosomal Peptides,Nonribosomal Peptides,Nonribosomal Peptides,Nonribosomal Peptides,Antibiotics,Nonribosomal Peptides,Antibiotics,Nonribosomal Peptides,Last resort for against drug-resistant pathogens,Nonribosomal Peptides,Hybrid NRP-PK,Nonribosomal Peptides,Hybrid NRP-PK - C-aminated,Nonribosomal Peptides,Hybrid NRP-PK - N-acylated,Nonribosomal Peptides,