Mining and identification of a biosynthetic gene cluster producing xanthocillin analogues from Penicillium chrysogenum MT-40, an endophytic fungus of Huperzia serrata

Abstract:

Xanthocillin is a unique natural product with an isonitrile group and shows remarkable antibacterial activity. In this study, the genome of an endophytic fungus Penicillium chrysogenum MT-40 isolated from Huperzia serrata was sequenced, and the gene clusters with the potential to synthesize xanthocillin analogues were mined by local BLAST and various bioinformatics analysis tools. As a result, a biosynthetic gene cluster (named for) responsible for the biosynthesis of xanthocillin analogues was identified by further heterologous expression of the key genes in Aspergillus oryzae NSAR1. Specifically, the ForB catalyzes the synthesis of 2-formamido-3-(4-hydroxyphenyl) acrylic acid, and the ForG catalyzes the dimerization of 2-formamido-3-(4-hydroxyphenyl) acrylic acid to produce the xanthocillin analogue N,N'-(1,4-bis (4-hydroxyphenyl) buta-1,3-diene-2,3-diyl) diformamide. The results reported here provide a reference for further discovery of xanthocillin analogues from fungi.