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Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase

文献类型：期刊论文

作者Li, Zhong5; Zhang, Lilan1; Xu, Kangwei4; Jiang, Yuanyuan5; Du, Jieke5; Zhang, Xingwang5; Meng, Ling-Hong2,3; Wu, Qile5; Du, Lei5; Li, Xiaoju5
刊名NATURE COMMUNICATIONS
出版日期2023-07-06
卷号14期号:1页码:15
DOI10.1038/s41467-023-39706-9
通讯作者Wu, Ruibo(wurb3@mail.sysu.edu.cn) ; Guo, Rey-Ting(guoreyting@hubu.edu.cn) ; Li, Shengying(lishengying@sdu.edu.cn)
英文摘要Diterpene synthase VenA catalyses the synthesis of venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. Here, the authors report crystal structures of apo- and holo-VenA, provide mechanistic insights into its substrate selectivity and promiscuity, and engineer VenA into a sesterterpene synthase. Diterpene synthase VenA is responsible for assembling venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. VenA also demonstrates substrate promiscuity by accepting geranyl pyrophosphate and farnesyl pyrophosphate as alternative substrates. Herein, we report the crystal structures of VenA in both apo form and holo form in complex with a trinuclear magnesium cluster and pyrophosphate group. Functional and structural investigations on the atypical (DSFVSD120)-D-115 motif of VenA, versus the canonical Asp-rich motif of DDXX(X)D/E, reveal that the absent second Asp of canonical motif is functionally replaced by Ser116 and Gln83, together with bioinformatics analysis identifying a hidden subclass of type I microbial terpene synthases. Further structural analysis, multiscale computational simulations, and structure-directed mutagenesis provide significant mechanistic insights into the substrate selectivity and catalytic promiscuity of VenA. Finally, VenA is semi-rationally engineered into a sesterterpene synthase to recognize the larger substrate geranylfarnesyl pyrophosphate.
WOS关键词MAIN-GROUP THERMOCHEMISTRY ; ACTIVE-SITE RESIDUES ; BIOSYNTHETIC MECHANISM ; PENTALENENE SYNTHASE ; TERPENE SYNTHASES ; NATURAL-PRODUCTS ; STRUCTURAL BASIS ; PI INTERACTIONS ; CYCLIZATION ; DYNAMICS
资助项目National Key Research and Development Program[2021YFA0911500] ; National Key Research and Development Program[2019YFA0905100] ; National Natural Science Foundation of China[32200017] ; National Natural Science Foundation of China[32025001] ; National Natural Science Foundation of China[32000039] ; National Natural Science Foundation of China[32170088] ; China National Postdoctoral Program for Innovative Talents[BX20220191] ; China Postdoctoral Science Foundation[2021M701989] ; China Postdoctoral Science Foundation[2022M710080] ; Shandong Provincial Postdoctoral Innovation Project[SDCX-ZG-202201005] ; Shandong Provincial Natural Science Foundation[ZR2019ZD20] ; Shandong Provincial Natural Science Foundation[ZR2022QC070]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:001026219000027
源URL[http://ir.qdio.ac.cn/handle/337002/182686]  
专题海洋研究所_实验海洋生物学重点实验室
通讯作者Wu, Ruibo; Guo, Rey-Ting; Li, Shengying
作者单位1.Hubei Univ, Hubei Collaborat Innovat Ctr Green Transformat Bi, Hubei Key Lab Ind Biotechnol, Hubei Hongshan Lab,Sch Life Sci,State Key Lab Bio, Wuhan, Hubei, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266237, Shandong, Peoples R China
3.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Nanhai Rd 7, Qingdao, Shandong, Peoples R China
4.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
5.Shandong Univ, State Key Lab Microbial Technol, 72 Binhai Rd, Qingdao 266237, Shandong, Peoples R China
推荐引用方式
GB/T 7714		 Li, Zhong,Zhang, Lilan,Xu, Kangwei,et al. Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase[J]. NATURE COMMUNICATIONS,2023,14(1):15.
APA Li, Zhong.,Zhang, Lilan.,Xu, Kangwei.,Jiang, Yuanyuan.,Du, Jieke.,...&Li, Shengying.(2023).Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase.NATURE COMMUNICATIONS,14(1),15.
MLA Li, Zhong,et al."Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase".NATURE COMMUNICATIONS 14.1(2023):15.

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来源：海洋研究所

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