Aromatic Halogenation by Using Bifunctional Flavin Reductase–Halogenase Fusion Enzymes. (22nd September 2017)

• Record Type: Journal Article
• Authors: Andorfer, Mary C.; Belsare, Ketaki D.; Girlich, Anna M.; Lewis, Jared C.
• Is Part Of: Chembiochem. Volume 18:Number 21(2017)
• Page Start: 2099
• Page End: 2103
• Publication Date: 2017-09-22
• Subjects: biocatalysis -- directed evolution -- enzymes -- halogenation -- regioselectivity; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700391
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: The remarkable site selectivity and broad substrate scope of flavin‐dependent halogenases (FDHs) has led to much interest in their potential as biocatalysts. Multiple engineering efforts have demonstrated that FDHs can be tuned for non‐native substrate scope and site selectivity. FDHs have also proven useful as in vivo biocatalysts and have been successfully incorporated into biosynthetic pathways to build new chlorinated aromatic compounds in several heterologous organisms. In both cases, reduced flavin cofactor, usually supplied by a separate flavin reductase (FR), is required. Herein, we report functional synthetic, fused FDH‐FR proteins containing various FDHs and FRs joined by different linkers. We show that FDH‐FR fusion proteins can increase product titers compared to the individual components for in vivo biocatalysis in Escherichia coli . Abstract : Come together : The remarkable site selectivity and broad substrate scope of engineered flavin‐dependent halogenases (FDHs) has led to much interest in their potential as biocatalysts. Herein, we report that synthetic, fused FDH–flavin reductase proteins can increase product titers compared to the individual components for biocatalysis in E. coli .