Importance of the following enzymes for the synthesis of drugs 1. introduction 2. penicillin acylase 3. lipase 4. oxidoreductase 5. transaminase 6. protease Conclusion References Thanks

1. INDUSTRIAL ENZYMES
UNIT- 10 BIOTECHNOLOGY IN PHARMACEUTICAL SCIENCES (NP- 510)
PRIYANSHA SINGH (PC- 226)
M.S. (PHARMACOLOGY & TOXICOLOGY)
NIPER- GUWAHATI

2. CONTENTS
Importance of the following enzymes in
enantioselective synthesis of a drugs/
intermediates
1. Penicillin Acyclase
2. Nitrilase
3. Lipase
4. Oxidoreductase
5. Protease
6. Transaminase

3. Enzymes
in enantioselective
synthesis of
drugs/ intermediates
• Enzymes are exceptional in performing
enantioselective reactions because of their high
chemo selectivity. Enantioselective enzymes act
one of the enantiomers (either R or S form) and
selectively transform it into the corresponding
product, whereas the other enantiomer remains
untouched.
• At this point, the product can readily be
separated from the other enantiomeric form of
the substrate. However, the conventional
method for resolution of racemates (i.e., the
enzymatic resolution of a racemic mixture of a
compound like amino acids or any synthetic or
natural biomolecule) results in 50% yield of
the required form of the isomers

4. APPLICATIONS OF PENICILLIN ACYLASE
Penicillin G acylase is used in the kinetic enantioselective acylation of the racemic azetidinone intermediate for
the synthesis of the carbacephalosporin antibiotic Loracarbef, an analogue of Cefaclor and anti-platelet agent
Xemilofiban.
A racemic mixture of ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate was resolved through an enantioselective
acylation catalyzed by penicillin G amidohydrolase (penicillin G acylase) from E. coli to yield the S-isomer, which
can be used as a chiral synthon for the synthesis of the antiplatelet agent Xemilofiban. The first step is the
synthesis of desilylated phenylacetamide racemic ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate, which is a
nonenzymatic step. In the second step, phenylacetamide is enzymatically hydrolyzed to produce (R)-amide in a
quantitative yield and (S)-amine with yield of 90%.

5. APPLICATIONS OF NITRILASE
• (S) and R- mandelic acids are the products of
mandelonitrile hydrolysis, they are important for
production of pharmaceutical & agricultural
intermediates
• Nitrilase is used in production of 4- cyano-3- hydroxybutyric acid from 3- hydroxy glutaronitrile for the
synthesis of cholesterol lowering drug LIPITOR (Atorvastatin)

6. APPLICATIONS
OF LIPASE
• Enantioselective esterification reaction of flurbiprofen with n- butanol
using Candida rugosa lipase enzyme

7. PHARMACEUTICAL INDUSTRY APPLICATIONS OF
PROTEASE
•A protease C from Bacillus subtilis was identified for enantioselective hydrolysis of a racemic ester . Hydrolysis was
achieved with the protease C in water to give R- succinic acid derivative for the further production of Brivaracetam.​

8. APPLICATION OF
TRANSAMINASE
• Biocatalytic route features direct
amination of prositagliptin ketone to
provide enantiopure sitagliptin, followed
by phosphate salt formation to provide
sitagliptin phosphate.
• (R)-3-amino-4-(2,4,5-triflurophenyl)
butanoic acid (3-ATfBA), a β-amino acid is
a crucial intermediate for the synthesis
of important antidiabetic drugs such as
sitagliptin, retaglptin and evogliptin.

9. APPLICATIONS OF OXIDOREDUCTASE
• One of the major applications of oxidoreductase is a pharmaceutical synthesis of 3,4-
dihydroxylphenyl alanine (DOPA), which is employed in the treatment of Parkinson’s
disease and the industrial process that synthesizes DOPA make use of the
oxidoreductase polyphenol oxidase.
• It has been reported that the enantioselective reduction of C-4-substituted 3,5-
dixocarboxylates can be carried out by using alcohol dehydrogenase
from Lactobacillus brevis (LBADH) over-expressed in E. coli.
• Laccase oxidoreductase can be employed to synthesize numerous complex medicinal
agents including triazolo(benzo)cycloalkyl thiadiazines, vinblastine, penicillin X dimer,
cephalosporin antibiotics, and dimerized vindo-line

10. CONCLUSION
Enzymatic processes have replaced the
conventional chemical-based methods for the
synthesis of many APIs such as the production
of different semi-synthetic antibiotics, active
enantiomers of drugs through kinetic
resolution, synthesis of enantiomerically pure
forms of amino acids (d- and l-amino acids)
and others.

11. REFERENCES
• Applications of Oxidoreductases- By Sandhya
Rani Gogoi DOI:10.5772/intechopen.94409
• Enzymes for pharmaceutical and
therapeutic applications- Gautam Kumar
Meghwanshi, Navpreet Kaur, Swati
Verma, Narendra Kumar Dabi, Abhishek
Vashistha, P. D. Charan, Praveen Purohit, H.S.
Bhandari, N. Bhojak & Rajender Kumar
• Biocatalysis: Enzymatic Synthesis for
Industrial Applications- Shuke Wu, Radka
Snajdrova, Jeffrey C. Moore, Kai Baldenius,
and Uwe Bornscheuer