Expression of a Colletotrichum polyketide synthase gene in Aspergillus nidulans leads to unexpected conjugates with a host metabolite

Heterologous expression of the putative 1,3,6,8-tetrahydroxynaphthalene synthase gene ChPKS from Colletotrichum higginsianum in Aspergillus nidulans led to the formation of at least eight new compounds. LC-MS analysis proved them as coupling products of 1,3,6,8-tetrahydroxynaphthalene with an intermediate of the cichorine biosynthetic pathway. Comprehensive NMR analysis confirmed the structures of the two predominant products higginidulans A and B. Deletion of the backbone gene of the cichorine pathway in host strain Aspergillus nidulans abolished the formation of higginidulans. Heterologous expression of ChPKS in the alternative Penicillium crustosum expression host resulted in the formation of the expected product 1,3,6,8-tetrahydroxynaphthalene, which was confirmed by acetylation and structural elucidation. This study provides an additional example of unexpected natural product formation by crosstalk of biosynthetic pathways derived from different species. Moreover, it highlights the importance of using alternative host systems for gene expression.