转自：康龙化成
Chemoenzymatic Cascade Synthesis ofMetal-chelating α-aminoAcids
Seth H. Young[a], James S. Andon[b], Jooyeon Lim[a], Mareena C.Franke[a], Daniel J. Weix[a], Tina Wang[a,b],Andrew R. Buller[a,b]*
[a] Department of Chemistry University ofWisconsin-Madison 1101 University Ave, Madison WI, USA
[b] Departmentof Biochemistry University of Wisconsin-Madison 443 Babcock Dr, Madison, WI,USA
—ChemCatChem, 2024, DOI:10.1002/cctc.202401958
Recommended by Yuquan Liu_PT
KEYWORDS:enzyme catalysis(反应类型), cascade（反应类型）, aldehyde, glycine(底物),amino acid (产物)
ABSTRACT: Metalchelating non-canonical amino acids (ncAAs) are uniquely functional building blocksfor proteins, peptide catalysts, and small molecule sensors. However, catalyticasymmetric approaches to synthesizing these molecules is hindered by theirfunctional group variability and intrinsic propensity to ligate metals. Inparticular, bipyridyl-L-alanine(BpyAla) is a highly sought ncAA butits complex, inefficient syntheses has limited utility. Here, we develop achemoenzymatic approach to efficiently construct BpyAla. Three enzymes that canbe produced in high titer together react to convert Gly and an aldehyde intothe corresponding β-hydroxy ncAA,which is subsequently deoxygenated. We explore approaches to synthesizing bi-arylaldehydes and show how the three-enzymatic cascade can access a range ofα-amino acids with bulky side chains, including a variety of metal chelatingamino acids. We show that newlyaccessible BpyAla analogs are compatible with existing amber suppression technology, whichwill enable future merging of traditional synthetic and biosynthetic approachesto tuning metal reactivity.
Previousbackground and this work
Time course analysis of completethree-enzyme cascade
Preparative-scalecascade synthesis of non-canonicalamino acids
Prof.Andrew R. Buller and Prof. Daniel J. Weix et al have reported a three-enzymecascade that converts readily available amino acids and syntheticallyaccessible aromatic biaryl metal chelating aldehydes to yieldnovel metal chelating amino acids. Each enzyme can be accessed in hightiter, >100 mg protein L-1 culture and this chemoenzymatic approach operateswith minimal workup. Further, the aromatic amino acids produced are easilyisolated through reverse-phase chromatography. This modular of chemoenzymaticapproach to BpyAla may lower the barriers to future work with this costly aminoacid. This work also enables development of artificial metalloenzymes tune theelectronic and steric environment of the metal chelating moiety. Promisingly, theyfound that two such BpyAlal analogs can be incorporated into a model protein using amber stop codonsuppression with the system previously developed for BpyAla. This work opensthe way for more streamlined production of this privileged ligand and enablesnew opportunities to develop tunable metal-chelating motifs in proteinengineering.
（转自：康龙化成）
