Erythromycin is a broad spectrum macrolide antibiotic that has been widely used to treat various bacterial infections, particularly those caused by Gram-positive bacteria and some Gram-negative bacteria. It was first isolated in 1952 from the soil bacterium Saccharopolyspora erythraea (formerly Streptomyces erythraeus) (Schonfeld & Kirst, 2002). Erythromycin works by binding to the 50S subunit of the bacterial ribosome, thereby inhibiting protein synthesis and leading to bacterial cell death.

Structure and Mechanism of Action

Erythromycin is characterized by its large macrolide ring, a 14-membered lactone ring, which is crucial for its antibiotic activity. Attached to this ring are two sugars: desosamine and cladinose. These sugar moieties are important for the drug’s solubility and activity.

The mechanism of action of erythromycin involves the inhibition of bacterial protein synthesis. By binding to the 50S ribosomal subunit, erythromycin blocks the translocation of peptides, effectively halting bacterial growth and proliferation. This binding interferes with the elongation of the peptide chain, thus preventing the synthesis of essential proteins required for bacterial survival.

Clinical Applications

Erythromycin is used to treat a variety of infections, including:

  • Respiratory tract infections (e.g., pneumonia, bronchitis)
  • Skin infections
  • Diphtheria
  • Pertussis (whooping cough)
  • Syphilis and other sexually transmitted infections
  • Gastrointestinal infections caused by susceptible strains of bacteria

Biochemical Synthesis of Erythromycin

Fermentation Process

The production of erythromycin involves a complex fermentation process, which includes the following steps:

  1. Strain Selection and Optimization: The bacterium Saccharopolyspora erythraea is cultivated under controlled conditions. Strain improvement through mutagenesis and genetic engineering can enhance erythromycin production.
  2. Inoculum Preparation: A small culture of S. erythraea is grown in seed media to prepare the inoculum. This inoculum is then used to initiate larger-scale fermentation.
  3. Fermentation: The inoculum is transferred to large fermentation tanks containing a nutrient-rich medium. The composition of the medium typically includes sources of carbon (e.g., glucose), nitrogen (e.g., peptone, yeast extract), and other essential nutrients. The fermentation process is carried out under specific conditions of pH, temperature, and aeration to optimize the growth of the bacteria and the production of erythromycin.
  4. Production Phase: During fermentation, S. erythraea produces erythromycin as a secondary metabolite. The fermentation process can take several days, and the production phase is carefully monitored to ensure maximum yield.
  5. Harvesting: Once the fermentation is complete, the culture broth containing erythromycin is harvested. The cells are separated from the broth by filtration or centrifugation.

Isolation and Purification

  1. Extraction: Erythromycin is extracted from the filtered fermentation broth using organic solvents. This process involves multiple extraction steps to ensure the efficient recovery of the antibiotic.
  2. Crystallization: The crude extract is concentrated, and erythromycin is precipitated out by adjusting the pH and adding specific solvents. Crystallization helps to remove impurities and concentrates the antibiotic.
  3. Purification: Further purification steps, such as recrystallization, chromatography, and lyophilization, are used to obtain highly pure erythromycin. These processes help to achieve the desired potency and quality for pharmaceutical use.

Genetic Modification

 The genes responsible for the biosynthesis of this antibiotic are clustered in the S. erythraea chromosome (Cortes et al., 1990; Donadio et al., 1991). These genes are further grouped into three required for:-

(1) formation of the molecule’s polyketide core, termed 6-deoxyerythronolide B (6dEB)

(2) deoxysugar biosynthesis and attachment

(3) additional tailoring and self-resistance.

There are different variants of erythromycin  but the most abundant and biologically active form is erythromycin A (Kibwage et al., 1985). 

Challenges in Erythromycin Production

The production of erythromycin faces several challenges, including:

  • Yield and Efficiency: Optimizing the fermentation conditions to maximize yield is crucial. This involves fine-tuning the growth medium, pH, temperature, and aeration.
  • Strain Improvement: Genetic manipulation of S. erythraea to increase erythromycin production is an ongoing research area. Techniques such as mutagenesis, recombinant DNA technology, and metabolic engineering are used to enhance strain productivity.
  • Purification: The purification process needs to be efficient to ensure high yield and purity of the final product. This often involves multiple steps, increasing the complexity and cost of production.

Semi-Synthetic Derivatives

Erythromycin has several semi-synthetic derivatives, developed to overcome some of its limitations, such as acid instability and poor pharmacokinetic properties. These derivatives include:

  • Clarithromycin: This derivative has improved acid stability and better oral bioavailability compared to erythromycin.
  • Azithromycin: Known for its extended half-life and enhanced tissue penetration, making it effective for shorter dosing regimens.
  • Dirithromycin: Designed to improve gastrointestinal tolerance and oral absorption.

Future Directions and Advances

Advancements in biotechnology and synthetic biology are paving the way for improved erythromycin production. Some promising areas include:

  • Metabolic Engineering: By modifying the metabolic pathways of S. erythraea, researchers aim to increase the flux towards erythromycin biosynthesis, thus enhancing yield.
  • Synthetic Biology: The use of synthetic biology techniques to engineer microorganisms with optimized biosynthetic pathways for erythromycin production holds great promise.
  • Continuous Fermentation: Implementing continuous fermentation processes could improve production efficiency and reduce costs compared to traditional batch fermentation.

Erythromycin remains a vital antibiotic in the fight against bacterial infections. Its production through biochemical synthesis involves complex fermentation and purification processes. Despite challenges, advances in genetic engineering, metabolic engineering, and synthetic biology are enhancing erythromycin production, ensuring its availability and efficacy in medical treatments. The development of semi-synthetic derivatives further extends its therapeutic potential, addressing limitations and expanding its clinical applications. As research progresses, the production and utilization of erythromycin and its derivatives are likely to become more efficient, sustainable, and effective in combating bacterial infections.


Cortes, J., Haydock, S. F., Roberts, G. A., Bevitt, D. J., & Leadlay, P. F. (1990). An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature348(6297), pp. 176-178.

Donadio, S., Staver, M. J., McAlpine, J. B., Swanson, S. J., & Katz, L. (1991). Modular organization of genes required for complex polyketide biosynthesis. Science252(5006), pp. 675-679

Kibwage, I. O., Hoogmartens, J., Roets, E., Vanderhaeghe, H., Verbist, L., Dubost, M., … & Levol, G. (1985). Antibacterial activities of erythromycins A, B, C, and D and some of their derivatives. Antimicrobial Agents and Chemotherapy28(5), pp. 630-633 (Article).

Schonfeld, W., & Kirst, H. A. (2002). Macrolide Antibiotics. Milestones in drug therapy. Birkhauser, Germany.

Visited 3 times, 1 visit(s) today

Be the first to comment

Leave a Reply

Your email address will not be published.


This site uses Akismet to reduce spam. Learn how your comment data is processed.