E-Book 3rd Congress

  • Metabolic engineering for drug discovery and development
  • Howra valinejad,1,* Issa layali,2 Erfan kashefi,3 Sajad cheraghali,4
    1. Department of Microbiology ,Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
    2. Department of Biochemistry and Biophysics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
    3. Department of Microbiology ,Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
    4. Department of Microbiology ,Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran


  • Introduction: Metabolic engineering, emerging in the early 1980s, stands at the forefront of manipulating biological systems via genetic alterations. This paper emphasizes recent strides, particularly the synergy between genetic engineering and biosynthetic chemistry, influencing the exploration of natural-product drugs. While natural products offer a bounty of successful drug leads, they often present challenges related to pharmacokinetics, production costs, and yield limitations from native hosts. Addressing these challenges involves innovative methodologies like organic chemistry, combinatorial synthesis, and leveraging enzymes, both in vitro and potentially within cellular environments. The balancing act of gene expression within heterologous pathways and the native metabolic milieu remains a core challenge in utilizing metabolic engineering for drug development
  • Methods: To comprehend the effects of metabolic engineering techniques, this study employed an integrative approach. Genetic manipulation, biosynthetic chemistry, and combinatorial synthesis were the primary methodologies utilized. Enzymatic processes were explored for in vitro functionalization of complex molecules, while the potential for cell-based combinatorial synthesis was also investigated. Introducing genes into biosynthetic pathways of heterologous hosts was a core aspect, demanding meticulous gene regulation to circumvent impediments in product synthesis and metabolic pathway bottlenecks.
  • Results: The convergence of genetic manipulation and redirection of metabolic pathways has not only facilitated the identification and understanding of biosynthetic pathways but also provided opportunities to streamline drug development pipelines. This has the potential to reduce the time and costs associated with bringing new drugs to market, offering hope for more accessible and affordable therapeutics, especially in regions where drug affordability remains a significant barrier.
  • Conclusion: Metabolic engineering has revolutionized drug discovery and development, particularly in the realm of natural-product drugs. The integration of genetic engineering and biosynthetic chemistry has significantly advanced our ability to harness natural compounds for therapeutic purposes. Despite the challenges related to optimizing pharmacological properties and production costs of natural products, metabolic engineering offers promising solutions.
  • Keywords: metabolic engineering drug discovery Biochemistry product natural product natural drug