bio synthetic approach

8/6/2019 Bio Synthetic Approach

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A Biosynthetic Approach ofA Biosynthetic Approach ofMedicinal Natural ProductsMedicinal Natural Products

55//2424//20112011 11Dr. Harish & Purvi kakraniDr. Harish & Purvi kakrani


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BiosynthesisBiosynthesis

Formation of a chemical compound by aliving organism..

BiogenesisBiogenesis::

Production or generation of livingProduction or generation of living

organisms from other living organisms.organisms from other living organisms.



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Organisms vary widely in their capacity

to synthesize and transform chemicals.For instance, plants are very efficientat synthesizing organic compounds via

photosynthesis from inorganicmaterials found in the environment,whilst other organisms such as animalsand microorganisms rely on obtaining

their raw materials in their diet, e.g. byconsuming plants.



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The pathways for generally modifying and

synthesizing carbohydrates, pr

oteins,

fats,and nucleic acids are found to be

essentially the same in all organisms,apart from minor variations.

These processes are collectively describedas primary metabolism, with thecompounds involved in the pathways

being termed primary metabolites.

Primary metabolism (| Biochemistry)



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Secondary metabolism,metabolicpathwaysthatarenotessential forgrowth,developmentor reproduction,

butthatusually haveecologicalfunction.

Secondary metabolites are those chemicalcompounds in organisms that are not directlyinvolved in the normal growth, developmentor reproduction of an organism. In this sensethey are "secondary".

Secondary MetabolismSecondary Metabolism



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Secondary metabolites, are found in only

specific organisms, or groups oforganisms, and are an expression of theindividuality of species.

Secondary metabolites are not necessarilyproduced under all conditions, and in thevast majority of cases the function of

these compounds and their benefit to theorganism is not yet known.



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The building blocksThe building blocks

The building blocks for secondarymetabolites are derived from primarymetabolism.

The number ofbuilding blocks neededis surprisingly few.



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The most important building blocks

employed in the biosynthesis ofsecondary metabolites are derivedfrom:

1. AcetylcoenzymeA (acetyl-CoA)

2. Shikimicacid

3. Mevalonicacid4. 1-deoxyxylulose 5-phosphate

5. Aminoacids



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11.. Acetate pathwayAcetate pathway

The form in which acetate is used in mostof its important biochemical reactions isacetyl coenzyme A (acetyl-CoA).

Acetyl-CoA is formed by oxidativedecarboxylation of the glycolytic pathwayproduct pyruvic acid.

Important secondary metabolites formed

from the acetate pathway includes:1. Phenols

2. Prostaglandins

3. Macrolide antibiotics55//2424//20112011 1010Dr. Harish & Purvi kakraniDr. Harish & Purvi kakrani


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Coenzyme ACoenzyme A:: present in all living cells thatpresent in all living cells that

functions as an acyl group carrier.functions as an acyl group carrier.

P

N

N

N

NH2

OP

O

O O

OH OH

NH

NH

RS

OH

OO

O

O OH

O

P

O

HOHO

CH3H3C N



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22..Shikimate pathwayShikimate pathway

Shikimic acid is produced from a combinationofphosphoenolpyruvate, a glycolyticpathway intermediate, and erythrose 4-

phosphate from the pentose phosphatepathway.

The shikimate pathway leads to a variety of:

1.

Phenols

2. Cinnamic acid derivatives

3. Lignans

4. Alkaloids55//2424//20112011 1212Dr. Harish & Purvi kakraniDr. Harish & Purvi kakrani


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33.. Mevalonate pathwayMevalonate pathway

Mevalonic acid is itselfformed fromthree moleculesofacetyl-CoA, butthe mevalonate pathway channelsacetate into a different series ofcompounds than does the acetatepathway.



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55. Amino acids pathway. Amino acids pathway

Peptides, proteins, alkaloids and manyantibiotics are derived from amino acids.

Intermediates from the glycolytic pathwayand the Krebs cycle are used inconstructing many of them.

The aromatic amino acids phenylalanine,tyrosine, and tryptophan are themselves

products

from the shikimate pathway.55//2424//20112011 1515Dr. Harish & Purvi kakraniDr. Harish & Purvi kakrani


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Secondary metabolites can be synthesizedby combining several building blocks of the

same type, or by using a mixture of differentbuilding blocks.

Many of secondary metabolites also containone or more sugar units in their structure.

Toappreciatehowanatural productiselaborated,itisofvaluetobeable:

1. To dissect its structure into the basic building

blocks from which it is made up.2. To propose how these are mechanisticallyjoined together.



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Oxygenatoms can be introduced andremoved by a variety ofprocesses, and

soare not considered in the initialanalysis, except as a pointer to anacetate or shikimate origin.

Relatively few building blocks areroutinely employed, and the followinglist includes those most frequently

encountered in producing the carbonand nitrogen skeleton of a naturalproduct.



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C1:the simplest of the building blocks iscomposed of a single carbon atom, usually inthe form of a methyl group, and mostfrequently it is attached tooxygen ornitrogen, but occasionally to carbon. It is

derivedfrom the

S-methyl

ofL

-methionine.

C2:A two-carbon unit may be supplied byacetyl-CoA. Acetyl-CoA is first convertedinto the more reactive malonyl-CoA beforeits incorporation.



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C5:the branched-chain C5 isoprene unit is afeature of compounds formed from

mevalonate or deoxyxylulose phosphate.

C6C3:this refers to a phenylpropyl unit andis obtained from the carbon skeleton of eitherL-phenylalanine or L-tyrosine.

C6C2N:again, this building block is formedfrom either L-phenylalanine or L-tyrosine.



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Indole.C2N: the third of the aromaticamino acids is L-tryptophan.

C4N: the C4N unit is usually found as aheterocyclic pyrrolidine system and is

produced from L-ornithine(non-proteinamino acid).

C5N: it is produced by using L-lysine andthe unit tends to be found as a piperidinering system.



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The construction mechanismsThe construction mechanisms

Natural product molecules arebiosynthesized by a sequence of reactionswhich are catalyzed by enzymes.

Enzymes have the power t

oeffect thesetransformations:

1. More efficiently and more rapidly than thechemical analogy.

2. Under very much milder conditions.3. Carry out reactions in a stereospecific

manner.



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