Structure Model‐Guided Reprogramming Enables Functional Interconversion of Phomactatriene and Verticillene Synthases
Abstract
Abstract Terpenoids represent the most structurally diverse class of natural products on Earth. Terpene synthases are key enzymes for constructing the complex and varied terpene skeletons by catalyzing the formation of multiple carbon–carbon bonds. Phomactatriene and verticillene family natural products are both classified as bicyclic diterpenoids, sharing a unique bicyclo[9.3.1]pentadecane skeleton. In this study, we used genome mining to identify the phomactatriene synthase SiPS from bacteria, together with two verticillene synthases, LxVS and AxVS. Our DFT calculations revealed that the rearrangement pathways for compounds in the phomactatriene and verticillene families follow a shared biosynthetic route. Furthermore, through comparative structural model analyses of the phomactatriene and verticillene synthases, we employed molecular modelling and site‐directed mutagenesis to facilitate functional interconversion between these distinct terpene synthases. This work enhances our understanding of terpene biosynthesis and the potential for engineering terpene synthases for biotechnological applications.
Article Details
Authors (10)
Li Zhang
Yinghan Chen
State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering
Yan Wang
Ao Zhu
State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Nanjing Drum Tower Hospital, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences
Yi Ling Hu
State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional Biomolecules Department of Neurology Nanjing Drum Tower Hospital Chemistry and Biomedicine Innovation Center (ChemBIC) School of Life Sciences Nanjing University Nanjing 210023 China
Xiao Ling Huang
State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Department of Neurology, Nanjing Drum Tower Hospital, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences Nanjing University Nanjing 210023 China
Qi Zhang
Yong Liang
Jing Shi
Hui Ming Ge
State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Nanjing Drum Tower Hospital, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences