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