TETRACYCLINE
PRODUCTION
AN OVERVIEW OF THE KEY STEPS AND MICROORGANISMS INVOLVED
INTRODUCTION
THIS PRESENTATION EXPLORES THE
DETAILED PRODUCTION PROCESS
OF TETRACYCLINE, A CRUCIAL
BROAD-SPECTRUM ANTIBIOTIC,
FOCUSING ON THE
MICROORGANISMS USED AND THE
FERMENTATION PROCESS INVOLVED.
TETRACYCLINE
• TETRACYCLINE IS A BROAD-SPECTRUM ANTIBIOTIC
USED TO TREAT BACTERIAL INFECTIONS SUCH AS
ACNE, RESPIRATORY TRACT INFECTIONS, URINARY
TRACT INFECTIONS, AND CERTAIN SEXUALLY
TRANSMITTED DISEASES.
• MOA- IT WORKS BY INHIBITING BACTERIAL PROTEIN
SYNTHESIS, PREVENTING BACTERIA FROM GROWING
AND MULTIPLYING. IT INHIBITS THE 30S RIBOSOMAL
MAIN PRODUCER:
STREPTOMYCES
AUREOFACIENS
STREPTOMYCES AUREOFACIENS IS THE PRIMARY
MICROORGANISM USED FOR TETRACYCLINE
PRODUCTION. THIS BACTERIUM IS WELL-KNOWN FOR
ITS ABILITY TO SYNTHESIZE A VARIETY OF ANTIBIOTICS
AS SECONDARY METABOLITES. ITS GENETIC TRAITS
MAKE IT A PREFERRED CHOICE FOR INDUSTRIAL
PRODUCTION, OFTEN OPTIMIZED THROUGH GENETIC
MODIFICATIONS TO ENHANCE YIELD AND
PRODUCTIVITY.
OTHER SPECIES:
STREPTOMYCES RIMOSUS,
STREPTOMYCES VIRIDIFACIENS
BESIDES STREPTOMYCES AUREOFACIENS, OTHER SPECIES LIKE
STREPTOMYCES RIMOSUS AND STREPTOMYCES VIRIDIFACIENS
ALSO CONTRIBUTE TO TETRACYCLINE PRODUCTION. THESE
ACTINOMYCETES HAVE UNIQUE PROPERTIES THAT MAY ALLOW
THEM TO PRODUCE DIFFERENT TETRACYCLINES OR HAVE
VARIATIONS IN YIELD AND POTENCY, WHICH IS EXPLORED IN
INDUSTRIAL SETTINGS.
GENETIC MODIFICATIONS
FOR YIELD
GENETIC MODIFICATIONS
ENHANCE THE YIELD OF
TETRACYCLINE BY OPTIMIZING
METABOLIC PATHWAYS AND
IMPROVING RESISTANCE TO
ENVIRONMENTAL STRESSES.
THESE MODIFICATIONS MAY
INCLUDE GENE EDITING
TECHNIQUES THAT INCREASE
ANTIBIOTIC PRODUCTION RATES
OR ALTER THE FERMENTATION
PROCESS TO MAXIMIZE
02
FERMENTATIO
N PROCESS
PREPARATION OF CULTURES
• ISOLATES ARE CARRIED ON WAKSMAN AGAR FOR THE ISOLATION OF SOIL
MICROORGANISMS (WAKSMAN, 1922) WITHOUT ADJUSTMENT OF PH, AND ARE
INCUBATED AT 30 C FOR A PERIOD OF 10 DAYS TO PERMIT GOOD
SPORULATION. THE FORMULA FOR THIS AGAR FOLLOWS (PER L):
• GLUCOSE, 10.0 G
• PEPTONE, 5.0 G
• MONOPOTASSIUM PHOSPHATE, 1.0 G
• MAGNESIUM SULFATE HEPTAHYDRATE, 0.5 G
• AGAR, 20.0 G.
MEDIA
PREPARATION
THE FERMENTATION MEDIUM MUST SUPPORT OPTIMAL
GROWTH AND ANTIBIOTIC PRODUCTION. TYPICAL
COMPONENTS INCLUDE:
• CARBON SOURCES: GLUCOSE, STARCH, OR MOLASSES.
• NITROGEN SOURCES: CORN STEEP LIQUOR, AMMONIUM
SALTS, OR SOY FLOUR.
• MINERAL SALTS: MAGNESIUM, CALCIUM, AND
PHOSPHATE.
• PRECURSORS: ENHANCING COMPOUNDS LIKE
CHLORTETRACYCLINE OR SODIUM CITRATE (FOR
IMPROVED YIELD)
•Type of Fermenter: Stirred Tank
Fermenter (STF) is commonly used.
•Fermentation Conditions:
• Temperature: 26–28°C
• pH: Initially around 6.0, adjusted
to optimize production.
• Aeration: High (1–2 vvm) to
support aerobic growth.
• Agitation: Stirring (100–300 rpm)
to maintain uniform mixing.
• Duration: 4–7 days.
During fermentation, Streptomyces
bacteria produce tetracycline as a
secondary metabolite.
ISOLATION AND
PURIFICATION OF
TETRACYCLINE
AFTER FERMENTATION, THE BROTH CONTAINS TETRACYCLINE ALONG WITH THE
MICROBIAL BIOMASS AND OTHER BYPRODUCTS.
THEREFORE, PURIFICATION AND RECOVERY OF THE PRODUCT IS NECESSARY.
1) FILTRATION AND CENTRIFUGATION- THE FERMENTED BROTH IS FILTERED AND
TO REMOVE MICROBIAL CELLS. WHILE CENTRIFUGATION HELPS IN SEPARATION
OF SOLIDS FROM LIQUID ANTIBIOTIC SOLUTION.
2)PH ADJUSTMENT AND SALT EXTRACTION- THE PH IS ADJUSTED TO 9-10
(ALKALINE) TO DISSOLVE TETRACYCLINE INTO ORGANIC SOLVENTS LIKE
BUTANOL. THEN THE SOLUTION IS ACIDIFIED (PH- 2 TO 3) TO PRECIPITATE
TETRACYCLINE.
3)CRYSTALLIZATION
4) FURTHER PURIFICATION DONE BY HPLC
(CHROMATOGRAPHY)
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