Synthesis and recycling of the mycobacterial cell envelope

[Display omitted] •The unique mycobacterial cell wall is a layered structure of carbohydrates and lipids.•The architecture and biosynthesis of the cell wall have largely been elucidated.•Increasing evidence indicates that each cell wall layer is remodelled and recycled.•There are opportunities to discover new essential enzymes in cell wall metabolism.•Cell wall metabolism is a validated source of targets for tuberculosis drug discovery. Mycobacterium tuberculosis (Mtb), the causative agent of the disease tuberculosis, is a recognised global health concern. The efficacy of the current treatment regime is under threat due to the emergence of antibiotic resistance, directing an urgent requirement for the discovery of new anti-tubercular agents and drug targets. The mycobacterial cell wall is a well-validated drug target for Mtb and is composed of three adaptive macromolecular structures, peptidoglycan, arabinogalactan and mycolic acids, an array of complex lipids and carbohydrates. The majority of the enzymes involved in cell wall synthesis have been established, whilst studies directed towards the mechanisms of remodelling and recycling have been neglected. This review briefly describes mycobacterial cell wall synthesis, and focuses on aspects of remodelling and recycling, thus highlighting opportunities for future research.