Synfacts 2022; 18(05): 0541
DOI: 10.1055/s-0041-1737446
Organo- and Biocatalysis

Directed Evolution Toward Nonstandard Amino Acids by a Decarboxylative Aldol Reaction

Contributor(s):
Benjamin List
,
Marian Guillén
Ellis JM, Campbell ME, Kumar P, Geunes EP, Bingman CA, Buller AR. * University of Wisconsin–Madison, USA
Biocatalytic Synthesis of Non-Standard Amino Acids by a Decarboxylative Aldol Reaction.

Nat. Catal. 2022;
5: 136-143
DOI: 10.1038/s41929-022-00743-0.
 

Significance

Buller and co-workers disclose an enantioselective synthesis of γ-hydroxy amino acids catalyzed by engineered variants of a pyridoxal 5′-phosphate (PLP)-dependent enzyme. Various products of C–C bond-forming reactions were obtained in moderate to excellent yields and enantio­selectivities. The optimized enzyme UstDv2.0 is efficient in a whole-cell biocatalysis format, thereby eliminating the need for enzyme purification in gram-scale syntheses.


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Comment

Unlike other classic aldolases, UstD is capable of decarboxylating the side chain of pyridoxal-bound l-aspartate to form a putative nucleophilic enamine intermediate, which renders the ­enantioselective C–C bond-forming reaction effectively irreversible. An X-ray crystal-structure ana­lysis of UstDv2.0 revealed the active site and ­provides a foundation for probing the UstD ­mechanism. A broader scope of gram-scale whole-cell applications is anticipated.


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Publication History

Article published online:
20 April 2022

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