Scribd
Upload
556 views20 pages

Enzymatic Transformation: Divakara R Asst. Professor Dept. of Biotechnology The Oxoford College of Engineering Bengaluru

This document discusses artificial enzymes, which are synthetic molecules that mimic the function of natural enzymes. They are constructed through rational design, transition state analogue selection, or catalytic activity selection. Examples include derivatized proteins, cyclodextrins, calixarenes, polymers, and metal complexes. Artificial enzymes have applications in biological reactions, medical therapies, biosensing, green chemistry, and fuel production.

Uploaded by

Ramachandrappa Divakara
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
556 views20 pages

Enzymatic Transformation: Divakara R Asst. Professor Dept. of Biotechnology The Oxoford College of Engineering Bengaluru

This document discusses artificial enzymes, which are synthetic molecules that mimic the function of natural enzymes. They are constructed through rational design, transition state analogue selection, or catalytic activity selection. Examples include derivatized proteins, cyclodextrins, calixarenes, polymers, and metal complexes. Artificial enzymes have applications in biological reactions, medical therapies, biosensing, green chemistry, and fuel production.

Uploaded by

Ramachandrappa Divakara
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 20

Module 4

ENZYMATIC
TRANSFORMATION
Presented by:
DIVAKARA R
Asst. Professor
Dept. of Biotechnology
The Oxoford College of Engineering
Bengaluru
ARTIFICIAL ENZYMES
Traditional approaches to the synthesis of an artificial enzyme focused

on the rational design and synthesis of a complex catalyst molecule.


This approach of enzyme synthesis can help in the design and

construction of novel enzymes with enhanced catalytic and kinetic


properties.
But this type of approach is time consuming and the smallest flaw in

design can lead to catastrophic results.


Advances in the fields of molecular biology, biochemistry and more

recently combinatorial and polymer chemistry have all furnished


unique and often co-operative solutions to the synthesis of artificial
enzymes.
The rational design of macromolecular receptors with

appropriately positioned functional groups which recreate the


binding, catalytic efficiency and microenvironment of enzyme
active sites is the most logical approach for construction of
artificial enzymes.
The functional groups have been chosen to mimic the amino

acid residues known to be involved in the enzyme-catalysed


reaction.
An artificial enzyme is a synthetic, organic molecule or ion that

recreate some function of an enzyme.


These enzymes are mainly made up of organic molecules or

proteins tailored in such a way that they catalyse certain kinds of

reactions.
Generally artificial enzymes are constructed from synthetic

polymers or oligomers with incorporated enzyme activity.


They possess two structural entities, a substrate-binding site and

a catalytically effective site.


Like enzymes, they bind a transition state of a substrate in an

active site, and like enzymes they generally obey Michaelis-


Menten kinetics.
For one-substrate reaction the reaction sequence is given by
synzyme + S → (synzyme-S complex) → synzyme + P
Artificial enzymes are constructed by three different methods:
 i. Design approach
 ii. Transition state analogue-selection approach
 iii. Catalytic activity-selection approach
Design approach - A host molecule is designed with salient functionality

(often also present in the natural enzyme counterpart) which is expected to


be involved in catalysis of the chosen reaction. Catalytic cyclodextrins are
one such example.
Transition state analogue-selection approach - A library of hosts is

generated in the presence of a transition state analogue (TSA) and the best
host is then selected from the library. This latter approach has been
employed with considerable success in the field of catalytic antibodies and
has more recently inspired the process of `molecular imprinting' (vide
infra)
Catalytic activity-selection approach - This takes advantage of the

combinatorial chemistry revolution wherein a library of possible catalysts


is generated and screened directly for enzyme-like activity.
Examples of artificial enzymes
Derivatized proteins
Some synzymes are simply derivatised proteins.
An example is the derivatisation of myoglobin, the oxygen carrier in

muscle.
Myoglobin can be attached to [Ru(NH 3)5)3+] to its three histidine

residues located at its outer surface.


This derivatization converts it from a natural oxygen carrier to an

oxidase enzyme.
It catalyzes the oxidation of ascorbic acid whilst reducing molecular

oxygen at an efficiency almost as effective as natural ascorbate


oxidases.
Supramolecular enzyme mimics
i) Cyclodextrin derived synzymes

Cyclodextrins are cap structures with a hydrophilic exterior but a

hydrophobic interior.
They are naturally occurring toroidal molecules consisting of 6, 7, 8,

9 or 10 α-1, 4-linked D-glucose units joined head-to-tail in a ring (α-,

β-, γ-, δ- and ε-cyclodextrins, respectively).

They may be synthesized from starch by the cyclomaltodextrin

glucanotransferase (EC 2.4.1.19) from Bacillus macerans).

They differ in the diameter of their cavities (about 0.5-1 nm) but all

are about 0.7 nm deep.


These form hydrophobic pockets due to the glycosidic oxygen atoms

and inwards-facing C-H groups.


All the C-6 hydroxyl groups project to one end and all the C-2 and C-3

hydroxyl groups to the other.


Their overall characteristic is hydrophilic, being water soluble, but the

presence of their hydrophobic pocket enables them to bind hydrophobic


molecules of the appropriate size.
For example, a C-6 hydroxyl group of β-

cyclodextrin was covalently derivatised by an


activated pyridoxal coenzyme. If pyridoxal is
anchored in the interior the cyclodextrin
shows transaminase activity. The resulting
synzyme not only acted as a transaminase but PLP-derivatized CD

also showed stereoselectivity for the L-amino


acids.
β-cyclodextrin bis-imidazoles to mimic

Ribonuclease A
Uridyl-uridine lyase
Glutathione peroxidase synzyme Imidazole-derivatized CD
ii) Calixarenes
These are another type of supramolecule

with hydrophobic cavities.


Calixarene is a cyclic oligomer based on

the hydroxyalkylation product of a p-


alkyl phenol and formaldehyde
The word calixarene is derived from calix

because this type of molecule resembles a


vase and the word arene refers to the
aromatic building block.
Calixarene are efficient Na+ ionophores and are potentially

used in chemical sensors.


They also form complexes with Cadmium, lead , lanthanides

and actinides.
The cavities of calixarene bind to small molecules or ions,

enabling them to be used as ligands to form a wide range of


complexes
It can be used for the synthesis of acyltransferase, ATPase

synzymes, aldolase, Ribonuclease A, carbonic anhydrase


synzymes etc.
Polymers

Polyglutamic acid shows synzymic properties.

It acts as an esterase in much the same fashion as the acid proteases,

showing a bell-shaped pH-activity relationship, with optimum activity at

about pH 5.3, and Michaelis-Menten kinetics for the hydrolysis of

artificial substrate like 4-nitrophenyl acetate.


Polyethyleneimine

It is formed by polymerising ethyleneimine to give a highly

branched hydrophilic three-dimensional matrix. About 25% of the

resultant amines are primary, 50% secondary and 25% tertiary.


The primary amines may be alkylated to form a number of

derivatives.
If 40% of them are alkylated with 1-iodododecane to give

hydrophobic binding sites and the remainder alkylated with 4(5)-

chloromethylimidazole to give general acid-base catalytic sites,


The resultant synzyme has 27% of the activity of α-

chymotrypsin against 4-nitrophenyl esters. But, it has very low

esterase specificity
Metal complexes

SOD enzyme from mammalian mitochondria have Mn

complexes to act against free radicals.


Mimics of natural enzymes (synzymes) like Mn

complexes mimic the function of the natural enzyme.


The active site is composed of a trigonal bipyramidal

Mn complex with Mn in +2 or +3 oxidation state.


Several transition metal complexes,
especially manganese (III) complexes with porphyrin-
type ligands, have been reported to
be superoxide scavengers.
Metal ion complexes of functionalized 1,10-
phenanthroline derivatives has esterase activity.
Applications
Artificial enzymes are used in the biological reactions
i) Ribonuclease A synzymes are used in the hydrolysis of

RNA
ii) ATPase synzymes are used in the hydrolysis of ATP
iii) Restriction enzyme synzymes are used in the r-DNA

technology for the cleavage of DNA at a specific sites


iv) Enzyme-coenzyme mimics can be used for the

transamination reaction, redox reaction, etc.


Medical applications of artificial enzymes
i) SOD synzymes are used in the treatment of various

diseases and pathological conditions in order to reduce the


effect of ROIs
ii) Glutathione peroxidase are also used as antioxidant

enzyme
iii) Used in the construction of biosensors used in the

diagnostic and drug development laboratories


Enzyme mimics for green and sustainable chemistry

i) Polybenzylic ammonium chloride-based resins for sugar

dehydration
ii) “Diels–Alderase” for chemical synthesis

iii) Manganese metalloporphyrins as epoxidation catalysts

iv) Enzyme mimic–natural enzyme cascades for chemical

transformations
v) Enzyme mimics are used as anti-biofouling agents to prevent

biofouling in marine environment


Artificial enzymes in the production of fuels

i) Supramolecule–zeolite synzyme are used in the conversion of

methane into methanol


ii) Iron–carbonyl thiolate-based hydrogenase mimics for the

production of hydrogen gas

You might also like

pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy