The Mevalonate Pathway: Characteristics, Innovations, Applications, and Challenges in Biotechnology

The mevalonate pathway (MVA) is a central metabolic route responsible for the biosynthesis of isoprenoids, a vast and diverse class of biomolecules essential for cellular structure, signaling, and physiology. This review provides a comprehensive overview of the MVA pathway, addressing its distribution in different domains of life, evolutionary origins, and overall organization. We describe in detail its biochemical architecture, including enzymatic steps, catalytic mechanisms, structural characteristics, and multilayered regulatory strategies. In parallel, the methylerythritol phosphate pathway is presented as an alternative pathway to isoprenoid biosynthesis. The metabolic outputs of both pathways are explored, emphasizing the remarkable diversity of isoprenoid end products and their roles in membrane dynamics, protein modification, and cellular signaling. Furthermore, we analyze the biological functions and clinical relevance of the MVA pathway, including its involvement in human diseases and its variability in different kingdoms. The review also addresses recent advances in biotechnology, focusing on metabolic engineering and synthetic biology approaches for the microbial production of high-value isoprenoids. Finally, sustainable strategies for optimizing microbial cell factories and production processes are discussed, underscoring the growing importance of isoprenoid biosynthesis in industrial and pharmaceutical applications.