Sungeidines from a Non-canonical Enediyne Biosynthetic Pathway

• DOI: 10.1021/jacs.9b10086
• Publication Date: 2020-01-10T16:46:11Z
• Authors: Zhen Jie Low; Guang-Lei Ma; Hoa Thi Tran; Yike Zou; Juan Xiong; Limei Pang; Selbi Nuryyeva; Hong Ye; Jin-Feng Hu; K. N. Houk; Zhao-Xun Liang
• Keywords: :Biological sciences::Microbiology [Science]; Antibiotics, Antineoplastic; :Biological sciences::Biochemistry [Science]; Multigene Family; Natural Product; Enediynes; Biosynthesis; 01 natural sciences; Biosynthetic Pathways; 0104 chemical sciences

We report the genome-guided discovery of sungeidines, a class of microbial secondary metabolites with unique structural features. Despite evolutionary relationships with dynemicin-type enediynes, the sungeidines are produced by a biosynthetic gene cluster (BGC) that exhibits distinct differences from known enediyne BGCs. Our studies suggest that the sungeidines are assembled from two octaketide chains that are processed differently than those of the dynemicin-type enediynes. The biosynthesis also involves a unique activating sulfotransferase that promotes a dehydration reaction. The loss of genes, including a putative epoxidase gene, is likely to be the main cause of the divergence of the sungeidine pathway from other canonical enediyne pathways. The findings disclose the surprising evolvability of enediyne pathways and set the stage for characterizing the intriguing enzymatic steps in sungeidine biosynthesis.