Discovery and Characterization of a New Family of Diterpene Cyclases in Bacteria and Fungi

• Published in: Angewandte Chemie International Edition Vol. 56; no. 17; pp. 4749 - 4752
• Main Authors: Yang, Yan‐long, Zhang, Shasha, Ma, Ke, Xu, Yuxing, Tao, Qiaoqiao, Chen, Yihua, Chen, Juan, Guo, Shunxing, Ren, Jinwei, Wang, Wenzhao, Tao, Yong, Yin, Wen‐Bing, Liu, Hongwei
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 18.04.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Agaricales - chemistry; Agaricales - enzymology; Agaricales - genetics; Agaricales - metabolism; Amino acid sequence; Bacteria; Bacteria - chemistry; Bacteria - enzymology; Bacteria - genetics; Bacteria - metabolism; Basidiocarps; Basidiomycetes; Basidiomycota - chemistry; Basidiomycota - enzymology; Basidiomycota - genetics; Basidiomycota - metabolism; biosynthesis; Chemistry; Chemistry, Multidisciplinary; cyclases; Cyclization; Dimethylallyltranstransferase - genetics; Dimethylallyltranstransferase - metabolism; diterpenes; Diterpenes - chemistry; Diterpenes - metabolism; E coli; Escherichia coli; Fungi; Genomes; Multigene Family; natural products; Nucleotide sequence; Phylogeny; Physical Sciences; Science & Technology; UbiA; natural products; APOPTOSIS; METABOLITES; HERICIUM-ERINACEUM; biosynthesis; SYNTHASES; cyclases; diterpenes; IDENTIFICATION; UbiA; CHLOROFLEXUS-AURANTIACUS
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201700565

Diterpene cyclases from bacteria and basidiomycete fungi are seldom studied. Here, we presented the identification and verification of EriG, a member of the UbiA superfamily, as the enzyme responsible for the cyclization of the cyathane skeleton in the mushroom Hericium erinaceum. Genome mining using the EriG protein sequence as a probe led to the discovery of a new family of ubiquitous UbiA‐related diterpene cyclases in bacteria and fungi. We successfully characterized seven new diterpene cyclases from bacteria or basidiomycete fungi with the help of an engineered Escherichia coli strain and determined the structures of their corresponding products. A new diterpene with an unusual skeleton was generated during this process. The discovery of this new family of diterpene cyclases provides new insight into the UbiA superfamily. Full circle: EriG, a member of the UbiA superfamily, was identified as the enzyme responsible for the cyclization of the cyathane skeleton in the mushroom Hericium erinaceum. Genome mining using the EriG protein sequence led to the identification of a new family of widespread UbiA‐related diterpene cyclase genes in bacteria and fungi.