Cytochrome P450–catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis

Barry, Sarah M.; Kers, Johan A.; Johnson, Evan G.; Song, Lijiang; Aston, Philip; Patel, Bhumit A.; Krasnoff, Stuart B.; Crane, Brian R.; Gibson, Donna M.; Loria, Rosemary; Challis, Gregory L.

doi:10.1038/nchembio.1048

Cited by 181 publications

(246 citation statements)

References 18 publications

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“…The products of txtD and txtE conduct the nitration of the L-tryptophan moiety in thaxtomin biosynthesis (48,49). Although orthologs of txtD also occur in the nonpathogens S. avermitilis and S. venezuelae, this gene is not linked to txtE in these genomes.…”

Section: Figmentioning

confidence: 97%

Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species

Huguet‐Tapia

Lefébure

Badger

et al. 2016

Appl Environ Microbiol

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e Streptomyces spp. are highly differentiated actinomycetes with large, linear chromosomes that encode an arsenal of biologically active molecules and catabolic enzymes. Members of this genus are well equipped for life in nutrient-limited environments and are common soil saprophytes. Out of the hundreds of species in the genus Streptomyces, a small group has evolved the ability to infect plants. The recent availability of Streptomyces genome sequences, including four genomes of pathogenic species, provided an opportunity to characterize the gene content specific to these pathogens and to study phylogenetic relationships among them. Genome sequencing, comparative genomics, and phylogenetic analysis enabled us to discriminate pathogenic from saprophytic Streptomyces strains; moreover, we calculated that the pathogen-specific genome contains 4,662 orthologs. Phylogenetic reconstruction suggested that Streptomyces scabies and S. ipomoeae share an ancestor but that their biosynthetic clusters encoding the required virulence factor thaxtomin have diverged. In contrast, S. turgidiscabies and S. acidiscabies, two relatively unrelated pathogens, possess highly similar thaxtomin biosynthesis clusters, which suggests that the acquisition of these genes was through lateral gene transfer.

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Section: Figmentioning

confidence: 97%

Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species

Huguet‐Tapia

Lefébure

Badger

et al. 2016

Appl Environ Microbiol

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“…273 3.6.2.2.3 Aromatic nitration -rufomycin biosynthesis. One of the more unusual examples of a P450-catalysed transformation is the nitration of aromatic rings, which was initially identied in thaxtomin A biosynthesis in the nitration of a tryptophan residue (vide infra) 274 and has now also been reported in the nitration of a tyrosine residue in rufomycin biosynthesis. 275 A cyclic heptapeptide, rufomycin contains a number of unusual amino acid building blocks, with two -3-nitrotyrosine and trans 2-crotylglycine -utilising P450s in their formation.…”

Section: 269mentioning

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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“…Such noncanonical amino acids (NCAAs) have diverse applications in chemical biology (8), serve as intermediates in the synthesis of natural products (9,10), and are privileged scaffolds for the development of pharmaceuticals (11). Despite its natural ability to produce these desirable compounds, TrpS has enjoyed only limited application (7).…”

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confidence: 99%

Directed evolution of the tryptophan synthase β-subunit for stand-alone function recapitulates allosteric activation

Buller

Brinkmann‐Chen

Romney

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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257

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Enzymes in heteromeric, allosterically regulated complexes catalyze a rich array of chemical reactions. Separating the subunits of such complexes, however, often severely attenuates their catalytic activities, because they can no longer be activated by their protein partners. We used directed evolution to explore allosteric regulation as a source of latent catalytic potential using the β-subunit of tryptophan synthase from Pyrococcus furiosus (PfTrpB). As part of its native αββα complex, TrpB efficiently produces tryptophan and tryptophan analogs; activity drops considerably when it is used as a stand-alone catalyst without the α-subunit. Kinetic, spectroscopic, and X-ray crystallographic data show that this lost activity can be recovered by mutations that reproduce the effects of complexation with the α-subunit. The engineered PfTrpB is a powerful platform for production of Trp analogs and for further directed evolution to expand substrate and reaction scope.protein engineering | allostery | noncanonical amino acid | PLP

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Cytochrome P450–catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis

Cited by 181 publications

References 18 publications

Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species

Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species

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

Directed evolution of the tryptophan synthase β-subunit for stand-alone function recapitulates allosteric activation

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