Synthetic biology strategies for cyanobacterial systems to heterologously produce cyanobacterial natural products.

Covering: 2014 to 2024Cyanobacteria are prolific producers of bioactive natural products, including promising drug leads for FDA-approved cancer therapeutics. Advances in genome sequencing and computational tools have revealed a wealth of cyanobacterial biosynthetic gene clusters (BGCs). However, progress in genome-driven discovery has been hindered by challenges in manipulating native hosts and the limited availability of efficient heterologous expression platforms. This highlight focuses on recent synthetic biology innovations on cyanobacterial systems that address these obstacles, facilitating the production of diverse cyanobacterial natural product families. We discuss key features of widely used cyanobacterial chassis, such as Synechocystis sp. PCC 6803, Synechococcus elongatus UTEX 2973, Anabaena sp. PCC 7120, and emerging hosts. Advances in BGC cloning, combinatorial biosynthesis, transcriptional and translational regulation, and host engineering are also highlighted. Together, these synthetic biology developments provide a powerful framework for expanding cyanobacterial natural product discovery and production.