1. Primary metabolites Despite the extremely varied characteristics of living organisms, the pathways for generally modifying and synthesizing carbohydrates, proteins, fats, and nucleic acids are essentially the same in all organisms, apart from minor variations. These processes demonstrate the fundamental unity of all living matter, and are collectively described as primary metabolism, with the compounds involved in the pathways being termed primary metabolites. i.e. CHM411 Secondary metabolites are derived from primary metabolites but the genes and enzymes guiding biosynthesis vary from one organism to the next. Similar compounds occur within genuses and families

2. Origins of secondary metabolites Three major pathways to assembly of C skeleton Key precursors: Phosphoenol pyruvate (PEP)  shikimate pathway Acetyl CoA  acetate or mevalonate pathways N from amino acids  alkaloids

3. Building blocks (Fig. 2.2) C 1 – methyl groups C 2 – 2 carbon units from acetate pathway C 5 – isoprene C 6 C 3 - phenylpropanoid C 6 C 2 N – precursor to indole C 4 N & C 5 N – heterocyclic amines

4. C 1 : any molecule C 2 : Fatty acids Long chains on most molecules Polyketides Some aromatic rings C 5 : Isoprenoids chains & nonarom. rings C 6 C 3 : Phenylpropanoids

5. C 1 comes from SAM (S-adenosylmethionine) SAM can attach a methyl group to just about anything Methyls may be attached to C atoms on chains, rings, attached to oxygen (methoxy), attached to nitrogen (N-methyl)

6. Building blocks (Fig. 2.2) C 1 – methyl groups C 2 – 2 carbon units from acetate pathway C 5 – isoprene C 6 C 3 - phenylpropanoid C 6 C 2 N – precursor to indole C 4 N & C 5 N – heterocyclic amines

7. Origins of alkaloids (nitrogen-containing natural products) pyrrolidine piperidine

8. Identify the building blocks Most secondary metabolites are assembled from pieces coming from more than one biosynthetic pathway Can you figure out what the building blocks are in each structure? Analysis of building blocks helps us understand how the compound was made, what were the precursors?

9.  -carotene linolenic acidresveratrol

10. tetrahydrocannabinol 10-p-trans-coumaroyl-1S-dihydromonotropein  -bisabolene berberine

11. Newsweek article on new drug leads from marine bioprospectors U. Florida - H. Luesch, isolated anticancer drug largazole from cyanobacteria (Symploca) process known as “bioassay-guided fractionation” UMD alum Brian Murphy in search of anti-tuberculosis compounds thiazoles come from cyclization of cysteine

12. other cool stuff by cyanobacteria...