Chemistry Reference
In-Depth Information
The metabolic route used by bacteria, fungi, algae, parasites, and plants for the
biosynthesis of aromatic amino acids is the shikimate pathway. This pathway is not
found in animals or in humans, hence the products of this pathway represent essential
amino acids that must be obtained from the diet. The first enzyme involved is shiki-
mate kinase, an enzyme that catalyzes the ATP-dependent phosphorylation of shi-
kimate to form shikimate 3-phosphate. Shikimate 3-phosphate is then coupled with
phosphoenolpyruvate to give 5-enolpyruvylshikimate-3-phosphate via the enzyme
5-enolpyruvylshikimate-3-phosphate (EPSP) synthase as shown in Figure 4.9, where
the entire shikimate pathway is outlined. The 5-enolpyruvylshikimate-3-phosphate is
then transformed into chorismate by a chorismate synthase. The resulting prephenic
acid is synthesized by a rearrangement of chorismate. The prephenate is oxidatively
decarboxylated with retention of the hydroxyl group to give p - hydroxyphenyl-
pyruvate, which in turn undergoes transamination using glutamate as the nitrogen
source, to give two compounds: tyrosine and alpha keto-glutarate.
4.3 MEVALONATE PATHWAY
The mevalonate pathway is another important cellular pathway present in all
higher eukaryotes and many bacteria. It is important for the production of dimethyl-
allyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). These two
compounds serve as the basis for the biosynthesis of molecules used in processes
as diverse as terpenoid synthesis, protein prenylation, cell membrane mainte-
nance, hormones, protein anchoring, and N-glycosylation. They are also a part of
steroid biosynthesis.
4.4 POLYKETIDES
Polyketides are secondary metabolites generally derived from bacteria, fungi, plants,
and animals. These compounds form a large class of diverse compounds, which are
characterized by more than two carbonyl groups connected by single intervening
carbon atoms. Polyketides are usually biosynthesized through the decarboxylative
condensation of malonyl-CoA derived and extended units. The chemical structure
of the malonate ion is shown in Figure 4.10, created by a process known as Claisen
condensation. The condensation reaction allows for the formation of carbon-carbon
bonds. The reaction occurs between two esters (or in some cases between a carbonyl
and ester). When the reaction takes place under basic conditions a β-keto ester (or a
β-diketone) is formed.
Structurally, this diverse family of natural products possesses various biologi-
cal activities and pharmacological properties. There are numerous examples of
polyketide antibiotics, antifungals, and other biologically actives in commercial
use (e.g., erythromycin and tetracyclines are represented in Chapter 9) and they are
broadly divided into three classes:
Type I polyketides (e.g., macrolides)
Type II polyketides (e.g., aromatic molecules)
Type III polyketides (often small aromatic molecules produced by fungal species)
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