Autor: |
Wang X; State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China., Kong D; Biotechnology Research Center, Southwest University, No. 2 Tiansheng Road, Chongqing 400715, China., Huang T; State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China., Xu F; State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China., Tang MC; State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China., Deng Z; State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China., Lin S; State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.; Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. |
Abstrakt: |
β-Carboline (βC) alkaloids constitute a large family of indole alkaloids that exhibit diverse pharmacological properties, such as antitumor, antiviral, antiparasitic, and antimicrobial activities. Here, we report that a flavoprotein StnP2 catalyzes the dehydrogenation at C1-N2 of a tetrahydro-β-carboline (THβC) generating a 3,4-dihydro-β-carboline (DHβC), and the DHβC subsequently undergoes a spontaneous dehydrogenation to βC formation involved in the biosynthesis of the antitumor agent streptonigrin. Biochemical characterization showed that StnP2 catalyzed the highly regio- and stereo-selective dehydrogenation, and StnP2 exhibits promiscuity toward different THβCs. This study provides an alternative kind of enzyme catalyzing the biosynthesis of βC alkaloids and enhances the importance of flavoproteins. |