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Rationally engineering santalene synthase to readjust the component ratio of sandalwood oil.
Zha, Wenlong; Zhang, Fan; Shao, Jiaqi; Ma, Xingmei; Zhu, Jianxun; Sun, Pinghua; Wu, Ruibo; Zi, Jiachen.
Afiliación
  • Zha W; College of Pharmacy, Jinan University, 510632, Guangzhou, China.
  • Zhang F; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006, Guangzhou, China.
  • Shao J; College of Pharmacy, Jinan University, 510632, Guangzhou, China.
  • Ma X; College of Pharmacy, Jinan University, 510632, Guangzhou, China.
  • Zhu J; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 100050, Beijing, China.
  • Sun P; College of Pharmacy, Jinan University, 510632, Guangzhou, China.
  • Wu R; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006, Guangzhou, China. wurb3@mail.sysu.edu.cn.
  • Zi J; College of Pharmacy, Jinan University, 510632, Guangzhou, China. zijiachen@imm.ac.cn.
Nat Commun ; 13(1): 2508, 2022 05 06.
Article en En | MEDLINE | ID: mdl-35523896
Plant essential oils (PEOs) are widely used in cosmetic and nutraceutical industries. The component ratios of PEOs determine their qualities. Controlling the component ratios is challenging in construction of PEO biotechnological platforms. Here, we explore the catalytic reaction pathways of both product-promiscuous and product-specific santalene synthases (i.e., SaSSy and SanSyn) by multiscale simulations. F441 of SanSyn is found as a key residue restricting the conformational dynamics of the intermediates, and thereby the direct deprotonation by the general base T298 dominantly produce α-santalene. The subsequent mutagenesis of this plastic residue leads to generation of a mutant enzyme SanSynF441V which can produce both α- and ß-santalenes. Through metabolic engineering efforts, the santalene/santalol titer reaches 704.2 mg/L and the component ratio well matches the ISO 3518:2002 standard. This study represents a paradigm of constructing biotechnological platforms of PEOs with desirable component ratios by the combination of metabolic and enzymatic engineering.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sesquiterpenos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sesquiterpenos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido