Only for education purpose

1. VS
Nidhi Parabhubhai Patel
20SS03MB004
Aromatic antibiotic
Bioprocess technology
SSMB8010
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2. VS

3. “The antibiotics with aromatic rings in their
structure are regarded as aromatic
antibiotics.”

4.  In a strict since, all the antibiotics containing aromatic
nuclei should be considered in this group.
 However, most authors prefer to treat the three
important antibiotics namely chloramphenicol, griseofulvin
and novobiocin in the category of aromatic antibiotics,
and the same is done in this book also.

5. Chloramphenicol
 Chloramphenicol is a broad spectrum antibiotic that
can act against Gram-positive and Gram- negative
bacteria, besides rickettsia, actinomycetes and
chlamydia.
 However, administration of chloramphenicol is
associated with side effects, the most significant
being damage to bone-marrow.
 As such, chloramphenicol is treated as a reserve
antibiotic and selectively used.
 Chloramphenicol binds to 50S ribosomal subunit and
blocks (peptidyltransferase reaction) protein
biosynthesis.

6. Dichloroacetyleamino moiety
Prpanodiol moiety
P-nitrophenyl moiety

7. Production of chloramphenicol
 Chloramphenicol can be produced by Streptomyces
venezuelae and S. omiyanesis.
 However, chemical synthesis is mostly preferred for the
commercial production of chloramphenicol.
Chloramphenicol is lipid-
soluble, allowing it to
diffuse through the
bacterial cell membrane.
It then reversibly binds to
the L16 protein of the 50S
subunit of bacterial
ribosomes, where transfer
of amino acids to growing
peptide chains is prevented
thus inhibiting peptide
bond formation and
subsequent protein
synthesis.

8. Uses of Chloramphanical
 Treat eye infection
 Sometimes ear infection

9. Griseofulvin
 Griseofulvin is an antibiotic that acts specifically
on fungi with chitinous cell walls.
 It is used in the treatment of various fungal
skin infections.
 Further, griseofulvin is also employed in the
treatment of plant diseases caused by Biotrytis
and Alternaria solani.
 Although the exact mechanism of action of
griseofulvin is not known, it is believed that
chitin biosynthesis is adversely affected.

10. Griseofulvin

11.  Commercial production of griseofulvin is carried out by
employing Penicillium patulum.
 The chemical synthesis is less frequently used due to
high cost.
 The fermentation is carried out by an aerobic submerged
process with a glucose rich medium.
 Nitrogen is supplied by sodium nitrate.
 The optimal conditions for fermentation are—
1) temperature 23-26°C
2) pH 6.8-7.3
3) aeration 0.8-1 vvm
4) period 7-10 days
Production of Griseofulvin

12. Manufacturing of Griseofulvin
Preparation of Media
 Medium:
Czapek Dox Medium
Chemicals:
Glucose – 0.5%
Sodium nitrate – 0.2%
Potassium hydrogen phosphate – 0.1%
Magnesium sulphate - 7𝑯𝟐𝑶 0.05%

13. Steps involved in the manufacturing
process
Pre treatment of fermentation broth
Fermentation
Filtration
Extraction
Decolorization
Isolation and separation
Precipitation and purification
1
2
3
4
5
6
7

14. 1.Fermentation
 The pH of Czapek-Dox medium was adjusted
between 6.0-7.2. The medium was dispensed in the
fermenter .
 The fresh sample of mycelial suspension of fungus
Peccillium griseofulvum from the fresh slope on
raper steep agar (Czapek-Dox medium + corn
steep+ agar) was obtained.
 The solution was autoclaved for 200 minutes at
120°C at 15lbs pressure and fermented for 14
days at 24°C.

15. 2.Pretraetment of
fermentation broth
 The broth is heated above 60°C for 20- 30minutes.
After heating, sufficient coagulation of material
occurs to produce a valuable improvement in
separation characteristics of the broth. The period
of heating may be short, 5-10 minutes at 80°C
having been found to provide a satisfactory increase
in filtration rate.

16. 3.Filtration
Drum covered with diatomaceous earth matter and
allowed to rotate under vacuum with half immersed
in the slurry tank. Small amount of coagulation
agent added to broth and pumped into the slurry
tank. As drum rotates in the slurry tank under
vacuum thin layer of coagulated particles adhere to
drum.
 The layer thickens to from cake. As the cake
portion in the drum comes to the upper region
which is not immersed in the liquid it is washed
with water and dewatered immediately by blowing
air over it.
Then before the dried portion is again immersed
into the liquid it is cut off from drum by knife.

17. 4.Extraction
 Griseofulvin is extracted in the cold acetone
when it is used as an extraction agent. The
extractions with the cold acetone may be carried
out with the efficiencies between 75-96% or
even up to 99.5%. the quantity of the solvent
used in the extraction at large scale production
should be kept minimum. The volume of acetone
should be 3-5 times of the mycelial felt.

18. 5.Decolorization
 The color of the extract can be improved by the
addition of calcium hydroxide usually 2.5-50
g/liter preferably 5- 30 g/liter.
 The pH of the extract should be above 10.
 It can be neutralize by the removal of lime or
by using mineral acid.

19. 6.Isolation and separation
 The impurities or waxy substances are removed by
washing the extract with a solvent in which
extract is immiscible and also griseofulvin is
insoluble.
 Hydrocarbon solvents, generally aliphatic
hydrocarbons such as hexane or petroleum
containing a high portion of hexane are in general
suitable for this step.

20.  Griseofulvin can be precipitated from the solvent
extract in various ways.
 One of the method is using the liquid solvent in
which griseofulvin is substantially insoluble.
 Griseofulvin non-solvent is preferably water.
 The alkaline water is more effective for the
removal of colored impurities present in the
crystals of the griseofulvin.
7.Precipitation and
Purification

21. 7.Precipitation and
Purification
 Water is made alkaline with ammonia or an alkali
metal carbonate or alkali metal hydroxide.
 The suitable pH is about 8.5.
 The purity of the precipitate is generally improved
by washing with a solvent for the small quantities
of impurities remaining.
 The suitable washing media are dry or wet
acetone, a lower alkanol for example methanol or
butanol.
 Marked purification is obtained with the use of
methanol for this step.

22. Uses of Griseofulvin
 Treat skin infection
 Fungal infection
Jockitch Athlete’s foot Ringworm
On scalp On fingernails On toenails

23. Thank you