Design of an in vitro biocatalytic cascade for the manufacture of islatravir

Autor:	Edward C. Sherer, Junyong Jo, Holst M. Halsey, Jack Liang, Niki R. Patel, Agustina Rodriguez-Granillo, Christopher C. Nawrat, Aaron M. Whittaker, Canada Keith A, Margie Borra-Garske, Nicholas M. Marshall, Kevin R. Campos, Anna Fryszkowska, Yingju Xu, Paul N. Devine, Shane T. Grosser, Grant S. Murphy, Jovana Nazor, Matthew D. Truppo, Benjamin F. Mann, Jeffrey C. Moore, Sandra A. Robaire, Gregory Hughes, Scott J. Novick, Da Duan, Jacob Forstater, Joshua N. Kolev, Deeptak Verma, Kevin M. Maloney, Oscar Alvizo, Mark A. Huffman, Li Xiao, Mark McLaughlin, Leo A. Joyce, Hao Yang
Rok vydání:	2019
Předmět:	Multidisciplinary Deoxyadenosines Chemistry Stereoisomerism Directed evolution Chemical synthesis Combinatorial chemistry In vitro Enzyme catalysis Pharmaceutical Preparations Cascade Biocatalysis Reverse Transcriptase Inhibitors Hiv treatment Biotechnology
Zdroj:	Science. 366:1255-1259
ISSN:	1095-9203 0036-8075
Popis:	Maximal efficiency from enzyme cascades Enzymes are highly selective catalysts that can be useful for specific transformations in organic synthesis. Huffman et al. combined designer enzymes in a multistep cascade reaction (see the Perspective by O'Reilly and Ryan). The approach eliminates purification steps, recycles expensive cofactors, and couples favorable and unfavorable reactions. With the target molecule islatravir, an experimental HIV drug, they optimized five enzymes by directed evolution to be compatible with unnatural substrates and stable in the reaction conditions. Stereochemical purity was amplified at every enzymatic step, and the final synthesis was both atom economical and efficient. Science , this issue p. 1255 ; see also p. 1199
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6857e349911e642ce3747f4ecbdaad7 https://doi.org/10.1126/science.aay8484 Zobrazit plný text záznamu Plný text ve formátu PDF