(129g) Enzymatic Cascade Synthesis of ?-Amino Acid Derivatives from Fatty Acids

β-Amino acids are important building blocks in bioactive compounds including potent chiral drugs and natural products. These non-proteinogenic amino acids have been shown to modulate the stability, bioactivity, and specificity of peptides and proteins, which underscores their significance in diverse biological processes. In this study, we have developed a novel, one-pot, metal-free, and environmentally friendly approach for the highly regioselective synthesis of β-amino acid derivatives. Our method utilized a unique combination of enzymes, including a P450 enzyme sourced from Bacillus subtilis, a fatty acid methyltransferase from M. marinum, an alcohol dehydrogenase from Micrococcus luteus, and a (S)-selective ω-aminotransferase from Vibrio fluvialis. This strategy involves the sequential C-H oxyfunctionalization of the fatty acid at the Cβ position followed by methylation, oxidation, and transamination reactions. Guided by machine learning algorithms, we have successfully optimized the efficiency of the methyltransferase, leading to significantly improved yields. The utilization of fatty acids sourced from renewable origins or microbial fermentation processes underscores the sustainability and biocompatibility of our approach in accessing β-amino acid derivatives. Our work holds immense promise for a broad range of pharmaceutical and industrial applications where synthesis of β-amino acid derivatives is demanded.