Primary metabolitesDespite 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

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

Building blocks (Fig. 2.2)

• C1 – methyl groups

• C2 – 2 carbon units from acetate pathway

• C5 – isoprene

• C6C3 - phenylpropanoid

• C6C2N – precursor to indole

• C4N & C5N – heterocyclic amines

C1: any molecule

C2: Fatty acidsLong chains on mostmoleculesPolyketidesSome aromatic rings

C5: Isoprenoidschains & nonarom. rings

C6C3: Phenylpropanoids

C1 comes from SAM (S-adenosylmethionine)

SAM can attach a methyl group to just about anythingMethyls may be attached to C atoms on chains, rings,attached to oxygen (methoxy), attached to nitrogen (N-methyl)

Building blocks (Fig. 2.2)

• C1 – methyl groups

• C2 – 2 carbon units from acetate pathway

• C5 – isoprene

• C6C3 - phenylpropanoid

• C6C2N – precursor to indole

• C4N & C5N – heterocyclic amines

Origins of alkaloids (nitrogen-containing natural products)

pyrrolidine

piperidine

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?

b-carotene

linolenic acidresveratrol

tetrahydrocannabinol10-p-trans-coumaroyl-1S-dihydromonotropein

a-bisabolene berberine

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

thiazolescome from cyclization of cysteine

other cool stuff by cyanobacteria...