@article {49968,
	title = {Total biocatalytic synthesis of capsaicinoids using ferulic acid: a versatile two-step strategy for natural product diversification},
	journal = {Angewandte Chemie-International Edition},
	volume = {64},
	year = {2025},
	month = {DEC },
	type = {Article},
	abstract = {<p>
	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 \&gt;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 \&gt;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 \&gt;88\%. A 50-mM enzymatic reaction afforded 95\% and 80\% conversion of vanillylamine and capsaicin, respectively.</p>
},
	keywords = {Capsaicinoids, Carboxylic acid reductase, Transaminase, Vanillylamine},
	issn = {1433-7851},
	doi = {10.1002/anie.202514504},
	author = {Khobragade, Taresh P. and Giri, Pritam and Patil, Mahesh D. and Joo, Sangwoo and Cho, Sunga and Kim, Yechan and Ghosh, Rohan and Jeong, Sanghun and Maeng, Minyeong and Song, Min-Ho and Park, Jeong-Min and Lee, Eun Ho and Keum, Young-Soo and Kang, Taek Jin and Heo, Yong-Seok and Yun, Hyungdon}
}
