TY - JOUR
T1 - Enzymatic strategies and biocatalysts for amide bond formation
T2 - Tricks of the trade outside of the ribosome
AU - Goswami, Anwesha
AU - Van Lanen, Steven G.
N1 - Publisher Copyright:
© The Royal Society of Chemistry 2015.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Amide bond-containing (ABC) biomolecules are some of the most intriguing and functionally significant natural products with unmatched utility in medicine, agriculture and biotechnology. The enzymatic formation of an amide bond is therefore a particularly interesting platform for engineering the synthesis of structurally diverse natural and unnatural ABC molecules for applications in drug discovery and molecular design. As such, efforts to unravel the mechanisms involved in carboxylate activation and substrate selection has led to the characterization of a number of structurally and functionally distinct protein families involved in amide bond synthesis. Unlike ribosomal synthesis and thio-templated synthesis using nonribosomal peptide synthetases, which couple the hydrolysis of phosphoanhydride bond(s) of ATP and proceed via an acyl-adenylate intermediate, here we discuss two mechanistically alternative strategies: ATP-dependent enzymes that generate acylphosphate intermediates and ATP-independent transacylation strategies. Several examples highlighting the function and synthetic utility of these amide bond-forming strategies are provided.
AB - Amide bond-containing (ABC) biomolecules are some of the most intriguing and functionally significant natural products with unmatched utility in medicine, agriculture and biotechnology. The enzymatic formation of an amide bond is therefore a particularly interesting platform for engineering the synthesis of structurally diverse natural and unnatural ABC molecules for applications in drug discovery and molecular design. As such, efforts to unravel the mechanisms involved in carboxylate activation and substrate selection has led to the characterization of a number of structurally and functionally distinct protein families involved in amide bond synthesis. Unlike ribosomal synthesis and thio-templated synthesis using nonribosomal peptide synthetases, which couple the hydrolysis of phosphoanhydride bond(s) of ATP and proceed via an acyl-adenylate intermediate, here we discuss two mechanistically alternative strategies: ATP-dependent enzymes that generate acylphosphate intermediates and ATP-independent transacylation strategies. Several examples highlighting the function and synthetic utility of these amide bond-forming strategies are provided.
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U2 - 10.1039/c4mb00627e
DO - 10.1039/c4mb00627e
M3 - Review article
C2 - 25418915
AN - SCOPUS:84921506516
SN - 1742-206X
VL - 11
SP - 338
EP - 353
JO - Molecular BioSystems
JF - Molecular BioSystems
IS - 2
ER -