Synthetic Biology and Metabolic Engineering for Natural Product Biosynthesis

Natural products (NPs) have been at the epicenter of drug discovery because of their structural diversity and bioactivity. However, natural extraction and chemical synthesis are some of the traditional methods that are usually hampered by low yields, insufficient sustainability or lack of scalability. The concept of synthetic biology and metabolic engineering presents a highly effective solution through the rational design, construction and optimization of biosynthetic pathways in a microbial host. Major directions involve the design of appropriate chassis organisms, improving precursor provision, co-factor regeneration, as well as the use of current tools for genome editing and pathway construction. Studies have highlighted the successful microbial biosynthesis of complex and pharmacologically important molecules, including antibiotics, antioxidants, anti-inflammatory agents, and anti-carcinogenic agents. These integrated technologies are collectively reshaping the biosynthesis of NPs, yielding efficiency, sustainability, and viability in industries. This chapter will present an overall perspective on the intersection of synthetic biology and metabolic engineering towards the improved microbial synthesis of NPs, with a focus on genome editing, pathway design, and cutting-edge technologies like artificial intelligence and cell-free systems.