Total Biocatalytic Synthesis of Capsaicinoids Using Ferulic Acid: A Versatile Two-Step Strategy for Natural Product...

Area of Science:

• Biocatalysis and Synthetic Biology
• Natural Product Synthesis
• Enzyme Engineering

Background:

• Capsaicinoids, active compounds in chili peppers, have diverse applications driving demand for sustainable production.
• Current capsaicinoid synthesis methods face challenges, necessitating innovative approaches.
• Developing efficient biocatalytic routes is crucial for sustainable capsaicinoid manufacturing.

Purpose of the Study:

• To report the total biocatalytic synthesis of structurally diverse capsaicinoids from bio-based ferulic acids.
• To characterize a novel transaminase (PPTA) from Phaeobacter porticola for vanillin conversion.
• To establish an enzymatic cascade for direct vanillylamine synthesis from ferulic acid.

Main Methods:

• Utilized X-ray crystallography to elucidate the structure and function of a novel transaminase (PPTA).
• Employed a multi-enzymatic cascade involving PPTA, phenolic acid decarboxylase (PAD), and aromatic dioxygenase (ADO).
• Integrated carboxylic acid reductases (CARs) for amide bond formation to synthesize capsaicinoids.

Main Results:

• PPTA demonstrated high conversion efficiency (>99%) for vanillin to vanillylamine at high concentrations (100-200 mM).
• The enzymatic cascade achieved >99% conversion of ferulic acid to vanillylamine.
• Structurally diverse capsaicinoids were synthesized with excellent conversions (72% to >88%) using the multi-enzymatic system.

Conclusions:

• This study presents a pioneering total biocatalytic synthesis of capsaicinoids from ferulic acid.
• The developed enzymatic cascade offers a sustainable and efficient method for producing diverse capsaicinoids.
• The findings pave the way for scalable and environmentally friendly capsaicinoid production.