Flavin-dependent halogenases involved in secondary metabolism in bacteria

Pée, Karl‐Heinz van; Patallo, Eugenio P.

doi:10.1007/s00253-005-0232-2

Cited by 163 publications

(157 citation statements)

References 55 publications

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“…A FADH 2 -dependent halogenase coding gene was situated inside the nrps2 gene cluster. Two absolute conserved motifs, GXGXXG in the N-terminal and WXWXIP in the C-terminal, were identified in the FADH 2 -dependent halogenase [24]. The nrps4 and nprs5 gene clusters had homologs in Streptomyces hygroscopicus subsp.…”

Section: Figurementioning

confidence: 99%

Assembly and features of secondary metabolite biosynthetic gene clusters in Streptomyces ansochromogenes

Zhong

Tian

Niu

et al. 2013

Sci. China Life Sci.

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A draft genome sequence of Streptomyces ansochromogenes 7100 was generated using 454 sequencing technology. In combination with local BLAST searches and gap filling techniques, a comprehensive antiSMASH-based method was adopted to assemble the secondary metabolite biosynthetic gene clusters in the draft genome of S. ansochromogenes. A total of at least 35 putative gene clusters were identified and assembled. Transcriptional analysis showed that 20 of the 35 gene clusters were expressed in either or all of the three different media tested, whereas the other 15 gene clusters were silent in all three different media. This study provides a comprehensive method to identify and assemble secondary metabolite biosynthetic gene clusters in draft genomes of Streptomyces, and will significantly promote functional studies of these secondary metabolite biosynthetic gene clusters.

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Section: Figurementioning

confidence: 99%

Assembly and features of secondary metabolite biosynthetic gene clusters in Streptomyces ansochromogenes

Zhong

Tian

Niu

et al. 2013

Sci. China Life Sci.

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“…123,[127][128][129] However crystallography of the tryptophan (22) 7-halogenase PrnA revealed that the substrate and flavin binding sites were spatially distinct, separated by a 10 Å tunnel, and therefore direct interaction of the substrate with the co-factor is not possible. 130,131 Mechanistic studies subsequently demonstrated that FAD-OOH (21) was generated prior to halogenation, even in absence of substrate, suggesting that nucleophilic attack of chloride on 21 may result in hypochlorous acid generation in the flavin-binding domain.…”

Section: 122-126mentioning

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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“…Tryptophan halogenases with regioselectivities for the 5-, 6-, and 7-position have been identified and characterised in the last few years from a number of different bacteria. [5] These flavin-dependent halogenases are a two-component system consisting of a flavin reductase that provides the reduced FAD required by the actual halogenase. [6] O'Connor and co-workers decided to use the tryptophan 7-halogenase RebH from rebeccamycin biosynthesis [7] and the tryptophan 5-halogenase PyrH from pyrroindomycin biosynthesis.…”

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confidence: 99%

Flavin-dependent halogenases involved in secondary metabolism in bacteria

Cited by 163 publications

References 55 publications

Assembly and features of secondary metabolite biosynthetic gene clusters in Streptomyces ansochromogenes

Assembly and features of secondary metabolite biosynthetic gene clusters in Streptomyces ansochromogenes

Development of Halogenase Enzymes for Use in Synthesis

Transformation with Tryptophan Halogenase Genes Leads to the Production of New Chlorinated Alkaloid Metabolites by a Medicinal Plant

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