Reporter systems in actinomycetes: Versatile tools for natural product discovery and production

Actinomycetes produce secondary metabolites that are crucial for medicine, health, and agriculture; however, their physiological and genetic characteristics present challenges for the discovery and production of these compounds. Reporter systems act as versatile molecular beacons in actinomycetes, linking genotype to phenotype by empowering the dissection of regulatory networks, the programmable design of genetic circuits, and high-throughput strain screening. This review highlights common reporter systems including resistance genes, pigment biosynthetic genes, fluorescent proteins, luciferases, and enzymatic reporter genes, along with their applications in enhancing metabolite production and activating silent gene clusters in actinomycetes. Beyond summarizing major reporter systems in actinomycetes, this review provides a comparative assessment of their strengths and limitations, offering guidance for tool selection and highlighting the need for broader, more versatile next-generation reporters integrated with AI-driven modeling to accelerate natural product discovery and production.