摘要
Xanthocillin具有显著的抗菌活性,结构中含有独特的异腈基。本文通过对蛇足石杉(Huperzia serrata)内生真菌产黄青霉菌(Penicillium chrysogenum)MT-40基因组的测序分析,利用本地BLAST等生物信息学分析工具挖掘具有合成xanthocillin类似物潜力的基因簇,结合米曲霉(Aspergillus oryzae)NSAR1异源表达技术实现基因簇中关键基因的功能鉴定。结果成功从内生真菌P.chrysogenum MT-40中发现一个合成xanthocillin类似物的生物合成基因簇(命名为for),for基因簇中的关键生物合成基因forB编码的异腈基合成酶可以催化合成2-formamido-3-(4-hydroxyphenyl)acrylic acid,基因forG编码的P450酶可以催化2-formamido-3-(4-hydroxyphenyl)acrylic acid的二聚化生成xanthocillin类似物N,N′-(1,4-bis(4-hydroxyphenyl)buta-1,3-diene-2,3-diyl)diformamide。本文研究结果为进一步从真菌中发现xanthocillin类似物提供参考。
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.
作者
王雯静
张蓓蓓
张明亮
张泽坤
王阳
葛祥宇
杜宇
张晓雪
刘晓
王娟
王晓晖
史社坡
WANG Wenjing;ZHANG Beibei;ZHANG Mingliang;ZHANG Zekun;WANG Yang;GE Xiangyu;DU Yu;ZHANG Xiaoxue;LIU Xiao;WANG Juan;WANG Xiaohui;SHI Shepo(Modern Research Center for Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《生物工程学报》
CAS
CSCD
北大核心
2023年第9期3814-3826,共13页
Chinese Journal of Biotechnology
基金
国家自然科学基金(82274042,81903405)。
