Seconadary Metabolites and Pathways

7/30/2019 Seconadary Metabolites and Pathways

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Biosynthesis of Secondary

Metabolites


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Secondary Metabolism

Secondary metabolism, metabolic pathways thatare not essential for growth, development orreproduction.

Secondary metabolites are those chemical

compounds in organisms that are not directly involvedin the normal growth, development or reproduction ofan organism. In this sense they are "secondary".

Secondary metabolites, are found in only specific

organisms, or groups of organisms, and are anexpression of the individuality of species.

Secondary metabolism (Natural productschemistry).
http://www.answers.com/topic/secondary-metabolitehttp://encyclopedia.thefreedictionary.com/chemical+compoundhttp://encyclopedia.thefreedictionary.com/chemical+compoundhttp://encyclopedia.thefreedictionary.com/organismhttp://encyclopedia.thefreedictionary.com/organismhttp://encyclopedia.thefreedictionary.com/chemical+compoundhttp://encyclopedia.thefreedictionary.com/chemical+compoundhttp://www.answers.com/topic/secondary-metabolite


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Secondary metabolites

Secondary metabolites are not necessarilyproduced under all conditions, and in the vastmajority of cases the function of thesecompounds and their benefit to the organism isnot yet known.

Some secondary metabolites are produced foreasily appreciated reasons, e.g.

1.As toxic materials providing defense againstpredators.

2.As volatile attractants towards the same or otherspecies.

3.As coloring agents to attract or warn other

species.


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The building blocks

The building blocks for secondary metabolites are

derived from primary metabolism.The number of building blocks needed issurprisingly few.

The most important building blocks employed inthe biosynthesis of secondary metabolites arederived from:

1. Acetyl coenzyme A (acetyl-CoA)

2. Shikimic acid3. Mevalonic acid

4. 1-deoxyxylulose-5-phosphate

5. Amino acids


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CO2 + H2O

Photosynthesis Glucose Carbohydrates

G

L

Y

C

OL

Y

S

I

S

Acetyl CoA

Citric Acid

Cycle

Fatty Acids

Lipids

Acetogenins

Terpenes

Steroids

Building Blocks

Amino Acids

Proteins

synthesis

enzymes

regulationNucleic

Acids

reproduction

Alkaloids

Phenyl-

propanoids

RNA DNA

PRIMARY METABOLISM

SECONDARY

METABOLISM

SECONDARY

METABOLISM

hn

CO2 + H2O + ATP

Flavonoids


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O

CH2OH

OH

OH

OH

OH

CO2

hn

photosynthesis

Glucose(6 carbons)

O

CH2OH

O

OH

OH

OH

O

CH2OH

O

OH

OH

O

CH2OH

O

OH

OH

starch nglycolysis

CH

CH2

OP

OH

CHO

C OP

CH2

COOH

C

CH2OP

O

CH2OH

phosphoenolpyruvate (PEP)(3 carbons)

CH3

C

O

SCoA

acetyl-

coenzymeA(2 carbons)

citric

acid

cycle

energy (ATP)

+ CO2 + H2O

CH3

C

O

CH2C

O

CH2

polyketides

acetogenins

lipidsfatty acids

mevalonic

acid

terpenes

steroids

carotenoids

CH OH

CH OH

CH2

OP

CHO

erythrose-

4-phosphate

COOH

OH OH

OH

shikimic

acid

NH2

COOH

anthranilic

acid

phenylalanine

tyrosine

alkaloids

tryptophan

oxalo-

acetate

lysine

ornithine

aspartic

acid

nicotinic

acid

phenylpropanes

glutamic acid

NH3


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1. Acetate pathway

The form in which acetate is used in most of itsimportant biochemical reactions is acetylcoenzyme A (acetyl-CoA).

Acetyl-CoA is formed by oxidative

decarboxylation of the glycolytic pathwayproduct pyruvic acid.

Important secondary metabolites formed fromthe acetate pathway includes:

1. Phenols2. Prostaglandins

3. Fatty acids

4. Macrolide antibioticsCH3

C

O

SCoA


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Coenzyme A: present in all living cells that

functions as an acyl group carrier.

R = H (Coenzyme A)R = CH3CO (acetyl-CoA).

R


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2. Shikimate pathway

Shikimic acid is produced from a combination of

phosphoenolpyruvate, a glycolytic pathway

intermediate, and erythrose 4-phosphate from the

pentose phosphate pathway.The shikimate pathway leads to a variety of:

1. Phenols

2. Cinnamic acid derivatives3. Lignans

4.Alkaloids

COOH

OH OH

OH


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3. Mevalonate pathway

Mevalonic acid is itself formed from three

molecules of acetyl-CoA, but the mevalonatepathway channels acetate into a different series

of compounds than does the acetate pathway.

4. Deoxyxylulose phosphate pathway

Deoxyxylulose phosphate arises from a

combination of two glycolytic pathway

intermediates, namely pyruvic acid and

glyceraldehyde 3-phosphate.The mevalonate and deoxyxylulose phosphate

pathways are together responsible for the

biosynthesis of a vast array ofterpenoid and steroid

metabolites.


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5. Amino acids pathway

Peptides, proteins, alkaloids and many

antibiotics are derived from amino acids.

Intermediates from the glycolytic pathway and

the Krebs cycle are used in constructing many

of them.

The aromatic amino acids phenylalanine,

tyrosine, and tryptophan are themselves

products from the shikimate pathway.


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The construction mechanismsNatural product molecules are biosynthesized by a

sequence of reactions which are catalyzed byenzymes.

Enzymes have the power to effect these

transformations:

1. More efficiently and more rapidly than the chemical analogy.

2. Under very much milder conditions.

3. Carry out reactions in a stereospecific manner

Secondary metabolites can be synthesized bycombining several building blocks of the same type, or

by using a mixture of different building blocks.

Many of secondary metabolites also contain one or

more sugar units in their structure.


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Some of the important reactions1.Alkylation reactions

2.Wagner-Meerwein rearrangements

3.Aldol and Claisen reactions

4.Schiff base formation and the Mannich reaction

5.Transamination

6.Decarboxylation reactions

7.Oxidation and reduction reactions8.Phenolic oxidative coupling

9.Glycosylation reactions


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Alkylation reactions

The C1 methyl building unit is supplied from L-

Methionine and is introduced by a nucleophilic

Substitution reaction.

In nature, the leaving group is enhanced by

converting L-methionine into S-

adenosylmethionine (SAM)


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Aldol and Claisen reactions


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Transamination


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Glycosylation reactionsFormation of glycosides and polysaccharides

require processes for attaching sugar units to asuitable atom of an aglycone a glycoside,

or to another sugar a polysaccharide.

The agent for glycosylation is a uridinediphosphosugar e.g. UDPglucose.


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Acetate pathway

Formation of phenols


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Simple phenols


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Shikimate pathway


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Papaverine biosynthesis

(An alkaloid)

The mevalonate and deoxyxylulose


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The mevalonate and deoxyxylulose

phosphate pathways

Terpenoids

Steroids


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OPPOPP

OPP

Mevalonic acid or Deoxyxylulose phosphate

Hemiterpenes (C5)DMAPP (C5) IPP (C5)

GPP (C10) Monoterpens & Iridoids (C10)

IPP

OPPFPP (C15) Sesquiterpenes (C15)

IPP

OPP

GGPP (C20)Diterpenes (C20)

2 x FPP Triterpenes (C30)2 x GGPP Tetraterpens (C40)

Steroids (C18-C30)

squalene

Bi th i f t


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Biosynthesis of monoterpenes

Essential oils

Fla onoids Shikimate + Acetate


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Flavonoids: Shikimate + Acetate

pathways

Seconadary Metabolites and Pathways

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