Abstract
Cercospora species have a global distribution and are best known as the causal agents of leaf spot diseases of many crops. Cercospora leaf spot (CLS) is an economically devastating disease of sugar beet caused by C. beticola. The C. beticola genome encodes 63 biosynthetic gene clusters, including the cercosporin toxin biosynthesis (CTB) cluster. Studies spanning nearly 60 years have shown that cercosporin is photoactivated, critical for disease development, and toxic to most organisms except Cercospora spp. themselves, which exhibit cercosporin auto-resistance. We show that the CTB gene cluster has experienced an unprecedented number of duplications, losses, and horizontal transfers across a spectrum of plant pathogenic fungi. Although cercosporin biosynthesis has been widely assumed to rely on the eight gene CTB cluster, our comparative genomic analysis revealed extensive gene collinearity adjacent to the established cluster in all CTB cluster-harboring species. We demonstrate that the CTB cluster is larger than previously recognized and includes the extracellular proteins fasciclin and laccase required for cercosporin biosynthesis and the final pathway enzyme that installs the unusual cercosporin methylenedioxy bridge. Additionally, the expanded cluster contains CFP, which contributes to cercosporin auto-resistance in C. beticola. Together, our results give new insight on the intricate evolution of the CTB cluster.
