Pharmacognosy antibiotics sources and productions, beta lactum antibiotics and productions and cephalosporin and monobactum antibiotics production B.pharm 6th semester B.pharm 6th semester ARYABHATT KNOWELDGE UNIVERSITY PATNA BIHAR AKU PATNA

1. CHEMISTRY OF BETA LACTUM ANTIBIOTIC
.
PHARMACOGNOSY
B.pharm 6th semester
A/C TO Aryabhatta Knowledge University, SYLLABUS
Public university in Patna, Bihar

48.  Beta lactum antibiotics
productiuon
1. Penicillin Production Process
• Penicillin production is done by fermentation
process in a fermenter by agitating the culture of
P.chrysogenum in a suitable condition.
• The whole process carried out is aerobic and the
method involved is fed-batch.

49. This fermentation process is of Penicillin G which involves
the following steps:
• 100ml medium with spores of P.chrysogenum strains is inoculated in
Erlenmeyer flask and is incubated at BOD incubator by placing them
on a rotatory shaker.
• After 4 days of incubation, the content along with two liters of
medium is transferred into a flask that contains four liters and again
incubates for two days.
• Then, the content is transferred into a stainless tank containing 500
ml of the medium that provides suitable conditions for fungal growth.
• After three days of incubation, the content is used for inoculation and
kept in a fermentor that is well equipped with optimum conditions.
• The content is filtered after six days of incubation which contains
penicillin.

50. • The penicillin is extracted into amyl or butyl acetate
and is transferred into an aqueous solution with
phosphate buffer.
• Acidify the extract and again re-extract penicillin
into butyl acetate
• In the solvent extract potassium acetated is added
to a crystallization tank to crystallize as a potassium
salt
• Crystals were recovered and further sterilization of
salt is done.

52. Penicillin
biosynthesis.

54. 2. Cephalosporin Production
• Acremonium chrysogenum also known as
Cephalosporiumacremonium is the industrial producer of
the antibiotic cephalosporinC, a beta-lactam antibiotic.
METHODS OF PRODUCTION
•Cephalosporin C production is an aerobic process,
carried out either by conventional or non-conventional
fermentation methods using free or immobilized fungi.
•Conventional mode of production: Cephalosporin c uses
either surface liquid or solid-state fermentation in a
batch bioreactor or continuous stirred tank reactor. But this
method is not much favorablefor cephalosporin c
production because of high probability of oxygen
Elimitation.

55. • Requirements of the fermentation process for
cephalosporinC production Fermentation medium
composition provides basic components required for
the fungus growth and for secondary
metabolitesproduction associated with their growth it
consisted of the following component.
• Carbon source i.e., glucose, sucrose, fructose, molasses,
and lactoseetc. It is required for morphological
di erentiation of the fungus. So,cephalosporin yield is
altered

56. • Organic and inorganic nitrogen sources i.e. peptone.
urea, meat extract, yeast extract, casein, beef extract,
ammonium sulphate,ammonium chloride, ammonium
nitrate, ammonium phosphate andpotassium nitrate
in uence mycelium di erentiation to swollen hyphae or
metabolically inactive arthrospores. uSING biosynthesis
of cephalosporin.

57. Requirments
• Trace elements or Essential vitamins:Aerobic conditions i.e.,
enough dissolved oxygen supply around40% or above.
• Sparging rings ensure continuous oxygen supply andits distribution
throughout fermentation process.• Appropriate bu er for
maintaining optimum pH.
• Small changes inthe pH can easily be detected by the pH meter.•
Optimum temperature maintained by owing water through
thejacket to promote fast growth of the fungus.
• A slight change in thetemperature can easily be detected using
temperature probes thatare sensitive to small temperature
variations.•
• Silicone oil to control foaming where necessary.
• Moisture.

58. Production Process:-
• Cephalosporin c production by Acremonium chrysogenum on the
fermentation medium at 28°C for 144 hours is characterized by the
rapid consumption of sucrose to form biomass at the beginning of the
process. pH of the medium was kept 7.2 and the temperature was
maintained at 28°C by passing water through the jacket. pH of the
broth was maintained by using 2 molar potassium hydroxides and 2
molar HCL.
• Dissolved oxygen was maintained above 30% saturation by agitation
and aeration.
• After the depletion of carbohydrate by the slow consumption of
sucrose during which most of the Cephalosporin c is produced is
called the idiophase and observed cell growth is insignificant.
Maximum cephalosporin c has been obtained at 120 h of
fermentation while highest cell growth occurs at 42 h of fermentation.

59. • Accumulation of secondary metabolites occurs in idiophase
after growth phase (tropophase) therefore called as
idiolites. Cephalosporin c is separated from the liquid broth
by the use of a number of separation and distillation
techniques in a sequential step wise manner depending on
the interactive chemical nature of the obtained product
Analysis/ obsevation : The dry cell weight was estimated
by centrifugation of 10 ml of fermentation broth, washed
twice with distilled water, recentrifuged and kept for drying
at 80°C till the constant weight.

60. biosynthesis

61. monobactum biosynthesis
• Alternative potential biosynthetic routes to
monobactam synthesis in sulfazecin.
• (a) biosynthetic gene cluster responsible for
the production of sulfazecin in P. acidophila.
• (b) possible routes of β-lactam formation in
sulfazecin.

63. THANKS FOR READING
SRIRAM SAWARNI
Founder of SAWARNCONCEPT
https://youtube.com/@SAWARNCONCEPTpharmacy?si=zuPiXe-wmvECDRHP