Lecture 1
Biocatalysis:
Biocatalysis is the chemical process through which enzymes or other biological catalysts
perform reactions between organic components. Biocatalysis has been used widely in the
pharmaceutical industry to make small molecule drugs. Otherwise could be decribed as a
catalyst from a biological origin.
Many different enzymes are used for countless different biological processes
● Ribozymes (Catalytic RNA)
○ Cleaving RNA
● Abzymes (Catalytic antibodies)
○ Stabilizing a transition state
● Synzymes/Chemsymes (Artificial enzymes)
○ Tailored molecules to catalyze certain reactions
● Designer enzymes
○ Binds and stabilizes transition states
Glucose isomerase: Production of high fructose corn syrup
Niytile hydratase: production of acrylamide from acrylanitrile
Invertase: Hydrolyzing sucrose
Enzymes are sensitive?
Partly true; enzymes do not like high T, solvents, extreme pH
But this is certainly not always true/problematic
Enzymes are expensive?
Production is nowadays very efficient, but still depends on enzyme
Enzymes are very efficient: little needed
Enzymes are only active on their natural substrates?
In most cases not true, and engineering is possible
Enzymes only work in natural environment?
In many cases not true, and engineering is possible
Benefits of biocatalysis:
- Very efficient
- Long lifetime, low energy demand
- Environmentally friendly
- Only need mild condition
- Reduces waste
- Can be used in cascades
- Can often catalyze non natural reactions
- Can often perform under non natural conditions
- Non toxic, biocompatible, renewable
- Production of complex compounds
- Can be ‘engineerd’
- Many reaction types are feasible
- Chemoselective, Regioselective, Enantioselective
,Disadvantagers of biocatalysis:
- Only available in one enantioneric form (L-amino acids)
- Not always available
- Narrow operation parameters/condition (temp, salt, solvent)
- Highest activity in water/buffer
- Sometimes require cofactors
- Inhibition effects
- May cause allergies
- Often not considered/forgotten
Green chemistry
Reducing waste, material usage, hazards, risks, energy and costs. Doing chemistry the way
nature does chemistry.
- Prevent waste
- Atom economy
- Less hazardous synthesis
- Designing benign chemicals (Not for BC)
- Usage of benign solvents and auxiliaries
- Design for energy efficiency
- use of renewable feedstocks
- Reduce derivatives
- Catalysis
- Design for degradation (Not in BC)
- Real-time analysis for pollution prevention
- Inherently benign chemistry for accident prevention
Biocatalysis conforms with 10 out of the 12 green chemistry principles
Lecture 2
Chiral molecule: A molecule that lacks an internal plane of symmetry and thus has a
non-superimposable mirror image. A chiral molecule and its mirror image are called
enantiomers. The enantiomers diplay virtually the identical physical properties except for the
direction of rotation of polarized light. The can exhibit distinct behavior when subjected to a
chiral environment, meaning that enantiomers can have differing pharmaceutical functions.
Pharmaceuticas therefore need to be enantiopure. This can be achieved in different ways.
Resolution of racemates: a mixture of enantiomers is converted to an optically pure
product with a theoretical 50 − 100% yield. This can be done through direct crystallization,
crystallization of diastereomeric salts, or chromatography to separate the enantiomers.
Another way is through kinetic resolution, thus eating away one of the enantiomers.
Enzymes are found to be most versatile for kinetic resolution and many fine chemicals
, producers employ lipases, proteases, esterases, acylases and amidases. There are multiple
ways of doing kinetic resolution:
a. Kinetic resolution: addition of a catalyst that only converts one enantiomer into product.
This has a 50% theoretical yield.
b. Dynamic kinetic resolution: addition of a catalyst that only converts one enantiomer into
product with the addition of an enzyme that converts one enantiomer into the other. This has
100% theoretical yield.
c. Dynamic kinetic asymmetric transformation: the enantiomers are first desymmetrized
into a non-chiral molecule. A catalyst then converts the desymmetrized molecule into
product. This has a 100% theoretical yield.
d. Direct enantio-convergent transformation: addition of a catalyst that converts one
enantiomer in with retention of configuration, whereas the other enantiomer is converted with
an inverse of configuration into the desired product. This has a 100% theoretical yield.
- Asymmetric synthesis: a prostereogenic (no chiral center) substrate is converted to
an optically pure product with 100% theoretical yield.
- Exploitation of the chiral pool: making use of chiral compounds (building blocks)
isolated from natural sources.
Tools in a chemists chiral toolbox:
Enzymatic resolution (and enzyme immobilisation)
o development of new (dynamic) kinetic resolutions
o co-catalysts/tandem reactions
• Enzymatic asymmetric synthesis
o new enzymes are needed (C-N, C-C, C-O,….)
o focus on C-C bond formation
• Systems Biocatalysis
o development of new enzymatic cascade reactions
Biocatalysis:
Biocatalysis is the chemical process through which enzymes or other biological catalysts
perform reactions between organic components. Biocatalysis has been used widely in the
pharmaceutical industry to make small molecule drugs. Otherwise could be decribed as a
catalyst from a biological origin.
Many different enzymes are used for countless different biological processes
● Ribozymes (Catalytic RNA)
○ Cleaving RNA
● Abzymes (Catalytic antibodies)
○ Stabilizing a transition state
● Synzymes/Chemsymes (Artificial enzymes)
○ Tailored molecules to catalyze certain reactions
● Designer enzymes
○ Binds and stabilizes transition states
Glucose isomerase: Production of high fructose corn syrup
Niytile hydratase: production of acrylamide from acrylanitrile
Invertase: Hydrolyzing sucrose
Enzymes are sensitive?
Partly true; enzymes do not like high T, solvents, extreme pH
But this is certainly not always true/problematic
Enzymes are expensive?
Production is nowadays very efficient, but still depends on enzyme
Enzymes are very efficient: little needed
Enzymes are only active on their natural substrates?
In most cases not true, and engineering is possible
Enzymes only work in natural environment?
In many cases not true, and engineering is possible
Benefits of biocatalysis:
- Very efficient
- Long lifetime, low energy demand
- Environmentally friendly
- Only need mild condition
- Reduces waste
- Can be used in cascades
- Can often catalyze non natural reactions
- Can often perform under non natural conditions
- Non toxic, biocompatible, renewable
- Production of complex compounds
- Can be ‘engineerd’
- Many reaction types are feasible
- Chemoselective, Regioselective, Enantioselective
,Disadvantagers of biocatalysis:
- Only available in one enantioneric form (L-amino acids)
- Not always available
- Narrow operation parameters/condition (temp, salt, solvent)
- Highest activity in water/buffer
- Sometimes require cofactors
- Inhibition effects
- May cause allergies
- Often not considered/forgotten
Green chemistry
Reducing waste, material usage, hazards, risks, energy and costs. Doing chemistry the way
nature does chemistry.
- Prevent waste
- Atom economy
- Less hazardous synthesis
- Designing benign chemicals (Not for BC)
- Usage of benign solvents and auxiliaries
- Design for energy efficiency
- use of renewable feedstocks
- Reduce derivatives
- Catalysis
- Design for degradation (Not in BC)
- Real-time analysis for pollution prevention
- Inherently benign chemistry for accident prevention
Biocatalysis conforms with 10 out of the 12 green chemistry principles
Lecture 2
Chiral molecule: A molecule that lacks an internal plane of symmetry and thus has a
non-superimposable mirror image. A chiral molecule and its mirror image are called
enantiomers. The enantiomers diplay virtually the identical physical properties except for the
direction of rotation of polarized light. The can exhibit distinct behavior when subjected to a
chiral environment, meaning that enantiomers can have differing pharmaceutical functions.
Pharmaceuticas therefore need to be enantiopure. This can be achieved in different ways.
Resolution of racemates: a mixture of enantiomers is converted to an optically pure
product with a theoretical 50 − 100% yield. This can be done through direct crystallization,
crystallization of diastereomeric salts, or chromatography to separate the enantiomers.
Another way is through kinetic resolution, thus eating away one of the enantiomers.
Enzymes are found to be most versatile for kinetic resolution and many fine chemicals
, producers employ lipases, proteases, esterases, acylases and amidases. There are multiple
ways of doing kinetic resolution:
a. Kinetic resolution: addition of a catalyst that only converts one enantiomer into product.
This has a 50% theoretical yield.
b. Dynamic kinetic resolution: addition of a catalyst that only converts one enantiomer into
product with the addition of an enzyme that converts one enantiomer into the other. This has
100% theoretical yield.
c. Dynamic kinetic asymmetric transformation: the enantiomers are first desymmetrized
into a non-chiral molecule. A catalyst then converts the desymmetrized molecule into
product. This has a 100% theoretical yield.
d. Direct enantio-convergent transformation: addition of a catalyst that converts one
enantiomer in with retention of configuration, whereas the other enantiomer is converted with
an inverse of configuration into the desired product. This has a 100% theoretical yield.
- Asymmetric synthesis: a prostereogenic (no chiral center) substrate is converted to
an optically pure product with 100% theoretical yield.
- Exploitation of the chiral pool: making use of chiral compounds (building blocks)
isolated from natural sources.
Tools in a chemists chiral toolbox:
Enzymatic resolution (and enzyme immobilisation)
o development of new (dynamic) kinetic resolutions
o co-catalysts/tandem reactions
• Enzymatic asymmetric synthesis
o new enzymes are needed (C-N, C-C, C-O,….)
o focus on C-C bond formation
• Systems Biocatalysis
o development of new enzymatic cascade reactions
