Structural and Computational Insights into the Noncanonical Aromatization in Fungal Polyketide Biosynthesis

Wang, Hang1,2,3; Peng, Chao1,2; Chen, Xiao-Xuan4,5; Wang, Hao-Yang4,5; Yang, Run1,2; Xiang, Hao1,2; Hu, Qiu-Fen1,2; Liu, Ling6; Chung, Lung Wa4,5; Matsuda, Yudai7; Wang, Wei-Guang1,2

2024-07-01

10.1021/acscatal.4c01043

ACS CATALYSIS   影响因子和分区

2155-5435

Aromatic polyketides, with their diverse structures and biological activities, have attracted significant scientific interest. Aromatization reactions are typically performed by aromatases and cyclases associated with bacterial type II polyketide synthases (PKSs) or product template and Claisen cyclase domains found in fungal type I nonreducing PKSs. Intriguingly, our recent study discovered a noncanonical aromatization mechanism involving a cupin domain-containing enzyme, StrC, in fungal alkyl salicylaldehyde derivative biosynthesis. Nevertheless, the catalytic function of StrC largely remained enigmatic. In this study, an in-depth in vitro characterization of StrC was performed to gain a better understanding of the reaction mechanism for aromatization. In addition, the X-ray crystal structure of StrC in the complex with a substrate analogue was obtained to elucidate the unique active site. Subsequent mutational experiments identified important amino acid residues for aromatase activity. Furthermore, a quantum mechanics study provided a plausible reaction mechanism for aromatization and highlighted the vital role of StrC in the biosynthetic process. Thus, our study unveils an unknown paradigm for aromatization in polyketide biosynthesis.

natural products biosynthesis polyketides aromatases cupin domain-containing enzymes

SCI ; EI

英语

通讯

National Natural Science Foundation of China["22377105","21907083","21933003","22193020","22193023","32022002","21977113"] ; National Natural Science Foundation of Yunnan Province and Jiangsu Province["202101AS070022","202401AV070003","BK20210434"] ; Yunnan Ten-thousand Talents Program[11301321] ; Shenzhen Nobel Prize Scientists Laboratory Project[C17783101] ; Guangdong Provincial Key Laboratory of Catalytic Chemistry[2020B121201002]

Chemistry

Chemistry, Physical

WOS:001282144900001

AMER CHEMICAL SOC

20242816677341

Aromatization ; Biochemistry ; Biosynthesis ; Catalysis ; Crystal structure ; Fungi ; Ketones ; Quantum theory

Biotechnology:461.8 ; Biochemistry:801.2 ; Chemical Reactions:802.2 ; Organic Compounds:804.1 ; Quantum Theory; Quantum Mechanics:931.4 ; Crystal Lattice:933.1.1

Web of Science

1.Yunnan Minzu Univ, State Ethn Affairs Commiss, Key Lab Nat Prod Synthet Biol Ethn Med Endophytes, Kunming 650031, Yunnan, Peoples R China
2.Yunnan Minzu Univ, Key Lab Chem Ethn Med Resources, Minist Educ, Kunming 650031, Yunnan, Peoples R China
3.China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Dept Chem, Shenzhen 518055, Peoples R China
5.Southern Univ Sci & Technol, Guangdong Prov Key Lab Catalysis, Shenzhen 518055, Peoples R China
6.Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China
7.City Univ Hong Kong, Dept Chem, Kowloon, Hong Kong, Peoples R China

Wang, Hang,Peng, Chao,Chen, Xiao-Xuan,et al. Structural and Computational Insights into the Noncanonical Aromatization in Fungal Polyketide Biosynthesis[J]. ACS CATALYSIS,2024,14:10796-10805.

Wang, Hang.,Peng, Chao.,Chen, Xiao-Xuan.,Wang, Hao-Yang.,Yang, Run.,...&Wang, Wei-Guang.(2024).Structural and Computational Insights into the Noncanonical Aromatization in Fungal Polyketide Biosynthesis.ACS CATALYSIS,14,10796-10805.

Wang, Hang,et al."Structural and Computational Insights into the Noncanonical Aromatization in Fungal Polyketide Biosynthesis".ACS CATALYSIS 14(2024):10796-10805.