Improvement of the stability and activity of the BPO-A1 haloperoxidase from Streptomyces aureofaciens by directed evolution

Yamada, R.; Higo, Tatsutoshi; Yoshikawa, Chisa; China, Hideyasu; Ogino, Hiroyasu

doi:10.1016/j.jbiotec.2014.10.030

Cited by 25 publications

(20 citation statements)

References 31 publications

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“…33, 34 Native and engineered versions of these proteins produce non-native halogenated compounds for use in stand-alone applications 35–38 or as synthetic intermediates to novel aryl/amino/alkoxo compounds. 39–42 With only a few exceptions, 43, 44 the flavin- and heme-utilizing systems are limited to transformation of aromatic substrates.…”

mentioning

confidence: 99%

Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate

Mitchell¹,

Dunham²,

Bergman³

et al. 2017

Biochemistry

102

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Enzymatic installation of chlorine/bromine upon unactivated carbon centers provides a versatile, selective, and environmentally-friendly alternative to chemical halogenation. Iron(II)- and 2-(oxo)-glutarate (FeII/2OG)-dependent halogenases are powerful biocatalysts that are capable of cleaving aliphatic C-H bonds to install useful functional groups, including halogens. Using the structure of the Fe/2OG halogenase, WelO5, in complex with its small-molecule substrate, we identified a similar N-acyl amino acid hydroxylase, SadA, and reprogrammed it to halogenate its substrate, thereby generating a new chiral haloalkyl center. The work high-lights the potential of FeII/2OG enzymes as platforms for development of novel stereospecific catalysts for late-stage C-H functionalization.

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mentioning

confidence: 99%

Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate

Mitchell¹,

Dunham²,

Bergman³

et al. 2017

Biochemistry

102

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“…50,77,[84][85][86] Vanadium-dependent haloperoxidases have been subject to mutagenesis to further improve their thermal stability as well as solvent and pH tolerance. 50,87,88 Structurally, the vanadium-dependent haloperoxidases are similar to the acid phosphatases, therefore it is not surprising that these enzymes can bind phosphate in place of vanadate and exhibit phosphatase activity. 89 Phosphate buffers can be therefore be useful for the crystallisation of the enzymes, but should be avoided in assays as phosphate can act as a competitive inhibitor.…”

Section: Vanadium-dependent Haloperoxidasesmentioning

confidence: 99%

Development of Halogenase Enzymes for Use in Synthesis

Latham

Brandenburger

Shepherd³

et al. 2017

Chem. Rev.

285

244

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Nature has evolved halogenase enzymes to regioselectively halogenate a diverse range of biosynthetic precursors, with the halogens introduced often having a profound effect on the biological activity of the resulting natural products. Synthetic endeavours to create non-natural bioactive small molecules for pharmaceutical and agrochemical applications have also arrived at a similar conclusion -halogens can dramatically improve the properties of organic molecules for selective modulation of biological targets in vivo. Consequently a high proportion of pharmaceuticals and agrochemicals on the market today possess halogens. Halogenated organic compounds are also common intermediates in synthesis and are particularly valuable in metal catalyzed cross-coupling reactions.Despite the potential utility of organohalogens, traditional non-enzymatic halogenation chemistry utilizes deleterious reagents and often lacks regiocontrol. Reliable, facile and cleaner methods for the regioselective halogenation of organic compounds are therefore essential in the development of economical and environmentally-friendly industrial processes. A potential avenue towards such methods is the use of halogenase enzymes, responsible for the biosynthesis of halogenated natural products, as biocatalysts. This review will discuss the advances towards this goal thus far, in addition to untapped potential sources of such biocatalysts and how further development of the enzymes may be focused in order to achieve the goal of industrial scale biohalogenation.

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“…Additionally, because the solid supports are washable and easily separated from reaction components, product recovery is simplified and the halogenase biocatalysts can be reused . Biocatalysts featuring both thermal stability as well as the capacity to function in organic solvents could be beneficial to large‐scale practical applications that require improved substrate solubility at higher temperatures or in organic solvent, longer catalyst lifetimes, or reactions performed at higher temperatures to increase reaction rates …”

Section: Enhancing Stability and Catalytic Efficiencymentioning

confidence: 99%

“…Mutagenesis can also enhance enzyme efficiency and stability (Scheme ). Directed evolution is one approach to generate enzymes with changed function and properties and does not require knowledge of the three‐dimensional structure of the enzyme . Wever's group reported the earliest example of directed evolution of a haloperoxidase .…”

Section: Enhancing Stability and Catalytic Efficiencymentioning

confidence: 99%

Halogenase Engineering for the Generation of New Natural Product Analogues

Brown

O’Connor

2015

ChemBioChem

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Halogenases catalyze the incorporation of halogen atoms into organic molecules. Given the importance that halogenation has on the biological activity of small molecules, these enzymes have been subjected to intense engineering efforts to make them more suitable for biotechnology applications. The ability to biohalogenate complex molecules provides, in principle, the opportunity for rapid generation of a series of analogues with new or improved properties. Here we discuss the potential and limitations of using halogenases as biocatalysts, including recent advances in engineering halogenases to generate halogenated natural product analogues.

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Improvement of the stability and activity of the BPO-A1 haloperoxidase from Streptomyces aureofaciens by directed evolution

Cited by 25 publications

References 31 publications

Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate

Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate

Development of Halogenase Enzymes for Use in Synthesis

Halogenase Engineering for the Generation of New Natural Product Analogues

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