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Cell‐Free Biosynthesis of ω‐Hydroxy Acids Boosted by a Synergistic Combination of Alcohol Dehydrogenases
Author(s) -
VelascoLozano Susana,
SantiagoArcos Javier,
Grazia Rubanu Maria,
LópezGallego Fernando
Publication year - 2022
Publication title -
chemsuschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.412
H-Index - 157
eISSN - 1864-564X
pISSN - 1864-5631
DOI - 10.1002/cssc.202200397
Subject(s) - biocatalysis , desymmetrization , chemistry , cofactor , alcohol , biosynthesis , combinatorial chemistry , catalysis , oxidative phosphorylation , enzyme , organic chemistry , enantioselective synthesis , biochemistry , reaction mechanism
The activity orchestration of an unprecedented cell‐free enzyme system with self‐sufficient cofactor recycling enables the stepwise transformation of aliphatic diols into ω‐hydroxy acids at the expense of molecular oxygen as electron acceptor. The efficiency of the biosynthetic route was maximized when two compatible alcohol dehydrogenases were selected as specialist biocatalysts for each one of the oxidative steps required for the oxidative lactonization of diols. The cell‐free system reached up to 100 % conversion using 100 mM of linear C 5 diols and performed the desymmetrization of prochiral branched diols into the corresponding ω‐hydroxy acids with an exquisite enantioselectivity ( ee >99 %). Green metrics demonstrate superior sustainability of this system compared to traditional metal catalysts and even to whole cells for the synthesis of 5‐hydroxypetanoic acid. Finally, the cell‐free system was assembled into a consortium of heterogeneous biocatalysts that allowed the enzyme reutilization. This cascade illustrates the potential of systems biocatalysis to access new heterofunctional molecules such as ω‐hydroxy acids.