Total Biocatalytic Synthesis of Capsaicinoids Using Ferulic Acid: A Versatile Two‐Step Strategy for Natural Product Diversification
Abstract
Abstract The wide‐ranging application of capsaicinoids, the active compounds in chili peppers, has driven increasing interest in the development of sustainable production strategies. However, capsaicinoid synthesis remains a challenge. The objective of this pioneering study is to report the total biocatalytic synthesis of structurally diverse capsaicinoids from bio‐based ferulic acids. An X‐ray crystallographic study elucidated the structural basis for the exceptional potential of a novel transaminase from Phaeobacter porticola (PPTA) to transform the highest ever reported concentration of vanillin (100–200 mM) to vanillylamine, with >99% conversion and modest conversion ranging from 48% to 79% for 300 to 500 mM substrate. Using PPTA in tandem with phenolic acid decarboxylase (PAD) and aromatic dioxygenase (ADO) further enabled the direct synthesis of vanillylamine from ferulic acid with >99% conversion. Furthermore, the integration of a multi‐enzymatic cascade with carboxylic acid reductases (CARs) successfully synthesized structurally diverse capsaicinoids via amide bond formation between vanillylamine and free fatty acids, with excellent conversions ranging from 72% to >88%. A 50‐mM enzymatic reaction afforded 95% and 80% conversion of vanillylamine and capsaicin, respectively.
Article Details
Authors (16)
Taresh P. Khobragade
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Pritam Giri
Mahesh D. Patil
Chemical Engineering and Process Development Division CSIR‐ National Chemical Laboratory Pune 411008 India
Sangwoo Joo
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Sunga Cho
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Yechan Kim
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Rohan Ghosh
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Sanghun Jeong
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Minyeong Maeng
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Min‐Ho Song
Department of Biological Environment Kangwon University Chuncheon Campus Chuncheon‐si Republic of Korea
Jeong‐Min Park
Department of Chemistry Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Eun Ho Lee
Department of Chemistry Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Young‐Soo Keum
Department of Crop Science Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Taek Jin Kang
Department of Chemical and Biochemical Engineering Dongguk University, Seoul Dongguk University Seoul 04620 Republic of Korea
Yong‐Seok Heo
Department of Chemistry Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea
Hyungdon Yun
Department of Systems Biotechnology Konkuk University 120 Neungdong‐ro, Gwangjin‐gu Seoul 05029 Republic of Korea