Stereo-selective synthesis of non-canonical γ-hydroxy-α-amino acids by enzymatic carbon–carbon bond formation

Abstract

Carbon-carbon (C-C) bond formation is the fundamental reaction type in organic synthesis. Biocatalytic methods for C-C bond formation have been limited to a few type of enzymes. In this report,...

Enzymatic Synthesis of Noncanonical α‐Amino Acids Containing γ‐Tertiary Alcohols

“…To understand this trait and estimate the activities of ApUstD toward different electrophiles, we determined the steady‐state kinetic parameters of ApUstD with 2 a , 2 b and benzaldehyde in parallel (Figure S6). ApUstD showed higher turnover numbers with 2 a ( k cat =50±8 min −1 ) and 2 b ( k cat =25±1 min −1 ) than with p ‐nitro benzaldehyde ( k cat =6.9±0.3 min −1 ) [15] . Notably, the catalytic efficiency of ApUstD with 2 a ( k cat / K M =183 M −1 s −1 ) and 2 b ( k cat / K M =4833 M −1 s −1 ) was 46‐fold and 1200‐fold higher than that with benzaldehyde ( k cat / K M =4 M −1 s −1 ), respectively.…”

“…ApUstD showed higher turnover numbers with 2 a (k cat = 50 � 8 min À 1 ) and 2 b (k cat = 25 � 1 min À 1 ) than with p-nitro benzaldehyde (k cat = 6.9 � 0.3 min À 1 ). [15] Notably, the catalytic efficiency of ApUstD with 2 a (k cat /K M = 183 M À 1 s À 1 ) and 2 b (k cat /K M = 4833 M À 1 s À 1 ) was 46-fold and 1200-fold higher than that with benzaldehyde (k cat /K M = 4 M À 1 s À 1 ), respectively. All the aforementioned results unveiled the remarkable activity, selectivity, and potential of ApUstD for the concise synthesis of multifunctionalized ncAAs.…”

“…[17] On the basis of previous mechanistic studies on PLPdependent enzymes, [18] it can be envisioned that a key enamine intermediate (EA) is first formed between the PLP cofactor and amino acids and further reacts with aldehydes or ketones to produce ncAAs. [14][15]19] Therefore, MD simulations were performed on the complex of the enzyme with EA and the ketone substrate, and QC calculations were then carried out on the basis of the representative conformation of MD simulations. In the MD simulations, both protonated and deprotonated forms were considered for the phosphate group of the PLP cofactor.…”

“…UstDs are pyridoxal 5′‐phosphate (PLP)‐dependent enzymes involved in the biosynthetic pathway of ribosomally synthesized and posttranslationally modified peptides, Ustiloxins A and B [14] . It was demonstrated in our previous study that UstD from Aspergillus pseudonomius (ApUstD) is capable of catalyzing the decarboxylative aldol reactions between L ‐aspartate and benzaldehyde derivatives, forming γ‐hydroxy‐α‐amino acids [15] . ApUstD has exhibited great activity, excellent selectivity and a broad scope of aldehydes.…”

Enzymatic Synthesis of Noncanonical α‐Amino Acids Containing γ‐Tertiary Alcohols

“…[14] It was demonstrated in our previous study that UstD from Aspergillus pseudonomius (ApUstD) is capable of catalyzing the decarboxylative aldol reactions between L -aspartate and benzaldehyde derivatives, forming γ-hydroxy-α-amino acids. [15] ApUstD has exhibited great activity, excellent selectivity and a broad scope of aldehydes. Based on these findings, we envision that ApUstD could promote the decarboxylative aldol reaction between Laspartate and ketones, resulting in a number of distinctive and complex multifunctionalized ncAAs with γ-tertiary alcohols.…”