Gene cluster conservation provides insight into cercosporin biosynthesis and extends production to the genus Colletotrichum

Abstract

SignificanceSpecies in the fungal genus Cercospora cause diseases in many important crops worldwide. Their success as pathogens is largely due to the secretion of cercosporin during infection. We report that the cercosporin toxin biosynthesis (CTB) gene cluster is ancient and was horizontally transferred to diverse fungal plant pathogens. Because our analyses revealed genes adjacent to the established CTB cluster with similar evolutionary trajectories, we evaluated their role in Cercospora beticola to show that four are necessary for cercosporin biosynthesis. Lastly, we confirmed that the apple pathogen Colletotrichum fioriniae produces cercosporin, the first case outside the family Mycosphaerellaceae. Other Colletotrichum plant pathogens also harbor the CTB cluster, which points to a wider role that this toxin may play in virulence.

Diversity in Fungal Intermolecular Phenol Coupling of Polyketides: Regioselective Laccase‐Based Systems

“…Slf14; elsinochrome A ( 12 ) in Parastagonospora nodorum SN15; and cercosporin ( 13 ; Scheme ) in Cercospora beticola , Cercospora zeae‐maydis , and Cercospora zeina (Figure S9 and Tables S15–S20). The laccase‐encoding gene CbCTB12 in C. beticola has been independently shown through knockouts to be involved in the biosynthesis of 13 …”

“…However, in some cases, the composition of the putative polyketide dimer BGCs suggests an involvement of FAS protein in the phenol‐coupling step. This observation is supported by knockouts of FAS proteins identified in the BGCs of aurofusarin in Fusarium graminearum and 13 in C. beticola . In the case of aurofusarin, knockout of the FAS protein encoding gene aurS abolished aurofusarin production, whereas its monomeric precursor 9 was still detected .…”

“…In the case of aurofusarin, knockout of the FAS protein encoding gene aurS abolished aurofusarin production, whereas its monomeric precursor 9 was still detected . Similarly, no dimer production was observed in Δ CbCTB11 mutants of C. beticola . Although FAS protein encoding genes were identified in the putative BGCs of the 8,8′‐linked dimers 2 , 7 , and aurofusarin, the BGCs of 6,6′‐linked 3 (and likely 5 ) did not contain such a gene.…”

“…The laccase system, either alone or in combination with auxiliary proteins, such as FAS or dirigent proteins, controls the regiochemical outcome of coupling reactions of the intermolecular homo‐ or heterodimerization. Similar systems have been reported for the biosynthesis of dinapinones in Talaromyces pinophilus FKI‐3864 and of 13 in C. beticola . Although our results conclusively demonstrate the ability of the laccase system to control the regiochemical outcome of phenol‐coupling reactions, possible stereochemical control and the role of FAS proteins require further examination.…”

The AVR4 effector is involved in cercosporin biosynthesis and likely affects the virulence of Cercospora cf. flagellaris on soybean

“…A biosynthetic pathway for cercosporin was also proposed (Chen et al , ). However, recent studies presented alternative biosynthetic pathways obtained by the characterization of metabolites from a series of biosynthetic pathway gene knockouts, as well as the discovery of several additional genes required for cercosporin biosynthesis through a comparative genomic and conserved gene cluster analysis (de Jonge et al ., , ; Newman and Townsend, ; Shim and Dunkle, ).…”