Structural, Functional, and Spectroscopic Characterization of the Substrate Scope of the Novel Nitrating Cytochrome P450 TxtE

Dodani, Sheel C.; Cahn, John W.; Heinisch, Tillmann; Brinkmann‐Chen, Sabine; McIntosh, Jason S.; Arnold, Frances H.

doi:10.1002/cbic.201402241

Cited by 50 publications

(120 citation statements)

References 25 publications

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“…350,351 Screening of a library of substrate analogs in which the amino, carboxylate, and indole moieties were all modified revealed molecular determinants for substrate binding and catalysis. 350 The TxtE substrate must possess an indole ring and accepts only slight modifications to this substructure. Furthermore, the amino and carboxylate groups are essential, and act as a hydrogen bond donor and acceptor, respectively, to properly position the indole moiety in the active site.…”

Section: N–o Bond Forming Enzymesmentioning

confidence: 99%

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

et al. 2017

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Natural products that contain functional groups with heteroatom-heteroatom linkages (X–X, where X = N, O, S, and P) are a small yet intriguing group of metabolites. The reactivity and diversity of these structural motifs has captured the interest of synthetic and biological chemists alike. Functional groups containing X–X bonds are found in all major classes of natural products and often impart significant biological activity. This review presents our current understanding of the biosynthetic logic and enzymatic chemistry involved in the construction of X–X bond containing functional groups within natural products. Elucidating and characterizing biosynthetic pathways that generate X–X bonds could both provide tools for biocatalysis and synthetic biology, as well as guide efforts to uncover new natural products containing these structural features.

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Section: N–o Bond Forming Enzymesmentioning

confidence: 99%

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

et al. 2017

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“…274 Subsequent studies have also shown that TxtE has tolerance for certain alternate substrates. 302 This reaction has been shown to require NO (generated by TxtD from arginine) and O 2 in addition to L-Trp, with electrons provided by a competent redox partner system from NAD(P)H (e.g. spinach Fdx/FdR) in order to generate a ferric peroxynitrite species as the reactive intermediate.…”

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confidence: 99%

Unrivalled diversity: the many roles and reactions of bacterial cytochromes P450 in secondary metabolism

et al. 2018

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The cytochromes P450 (P450s) are a superfamily of heme-containing monooxygenases that perform diverse catalytic roles in many species, including bacteria. The P450 superfamily is widely known for the hydroxylation of unactivated C-H bonds, but the diversity of reactions that P450s can perform vastly exceeds this undoubtedly impressive chemical transformation. Within bacteria, P450s play important roles in many biosynthetic and biodegradative processes that span a wide range of secondary metabolite pathways and present diverse chemical transformations. In this review, we aim to provide an overview of the range of chemical transformations that P450 enzymes can catalyse within bacterial secondary metabolism, with the intention to provide an important resource to aid in understanding of the potential roles of P450 enzymes within newly identified bacterial biosynthetic pathways. 1.Introduction to P450s 2.Chemistry of P450 enzymes 3.Bacterial biosynthesis pathways involving P450s 3.1Terpene metabolism 3.1. Battersby (1925Battersby ( -2018 to the molecular understanding of biosynthesis over the course of their careers.

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“…Mutation of the conserved axial cysteine to serine enabled further novel catalysis, C-H amination (88) and N-H insertion (89). Lastly, a cytochrome P450 oxidase was discovered that catalyzed nitration of tryptophan derivatives (90).…”

Section: Wwwannualreviewsorg • Biocatalysis: a Status Reportmentioning

confidence: 99%

Biocatalysis: A Status Report

Bommarius

2015

Annu. Rev. Chem. Biomol. Eng.

139

101

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This review describes the status of the fields of biocatalysts and enzymes, as well as existing drawbacks, and recent advances in the areas deemed to represent drawbacks. Although biocatalysts are often highly active and extremely selective, there are still drawbacks associated with biocatalysis as a generally applicable technique: the lack of designability of biocatalysts; their limits of stability; and the insufficient number of well-characterized, ready-to-use biocatalysts. There has been significant progress on the following fronts: (a) novel protein engineering tools, both experimental and computational, have significantly enhanced the toolbox for biocatalyst development. (b) The deactivation of biocatalysts under various stresses can be described quantitatively via rational models. There are several cases of spectacular leaps of stabilization after accumulating all stabilizing mutations found in earlier rounds. The concept that stabilization against one type of stress commonly also stabilizes against other types of stress is now experimentally considerably better founded than a few years ago.

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Structural, Functional, and Spectroscopic Characterization of the Substrate Scope of the Novel Nitrating Cytochrome P450 TxtE

Cited by 50 publications

References 25 publications

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

Unrivalled diversity: the many roles and reactions of bacterial cytochromes P450 in secondary metabolism

Biocatalysis: A Status Report

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