The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing

Mycolic acids (MAs) are unique and essential components of the Mycobacterium cell envelope, pivotal for its structural integrity, impermeability, and intrinsic antibiotic resistance. These properties that underpin mycobacterial pathogenicity also render the MA biosynthetic pathway a rich resource of targets for anti-tuberculosis drug discovery. Concurrently, in the realm of industrial biotechnology, engineered non-pathogenic mycobacteria are being optimized for steroid drug bioproduction through strategic modulation of the MA pathway to enhance cell permeability and boost the yield of desired products. This review systematically delineates the MA biosynthetic pathway and its critical enzymes. It further summarizes recent progress in developing anti-tuberculosis therapeutics that inhibit these enzymes and discusses innovative engineering strategies that harness the same pathway of non-pathogenic mycobacteria for green steroid drug manufacturing. By bridging these two distinct fields, the review provides a holistic perspective and novel insights for advancing both infectious disease control and sustainable pharmaceutical production.