Geranylation of Cyclic Dipeptides by the Dimethylallyl Transferase AnaPT Resulting in a Shift of Prenylation Position on the Indole Ring

Pockrandt, Daniel; Li, Shu-Ming

doi:10.1002/cbic.201300372

Cited by 19 publications

(25 citation statements)

References 30 publications

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“…[9,11,13,15] In contrast, they show high promiscuity for the aromatic substrate and accept a large number of tryptophan derivatives. [9,11,16,17] FgaPT2 and 7-DMATS even used hydroxynaphthalenes as prenyl acceptors; [18] these are natural substrates of prenyltransferases of the CloQ/NphB group, from both bacteria and fungi.…”

Section: Introductionmentioning

confidence: 89%

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Biochemical Investigations of Two 6‐DMATS Enzymes from Streptomyces Reveal New Features of L‐Tryptophan Prenyltransferases

Winkelblech

2014

ChemBioChem

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Two putative prenyltransferase genes, SAML0654 and Strvi8510, were identified in Streptomyces ambofaciens and Streptomyces violaceusniger, respectively. Their deduced products share 63% sequence identity. Biochemical investigations with recombinant proteins demonstrated that L-tryptophan and derivatives, including D-tryptophan, 4-, 5-, 6- and 7-methyl-dl-tryptophan, were well accepted by both enzymes in the presence of DMAPP. Structural elucidation of the isolated products revealed regiospecific prenylation at C-6 of the indole ring and proved unequivocally the identification of two very similar 6-dimethylallyltryptophan synthases (6-DMATS). Detailed biochemical investigations with SAML0654 proved L-tryptophan to be the best substrate (K(m) 18 μm, turnover 0.3 s(-1)). Incubation with different prenyl donors showed that they also accepted GPP and catalyzed the same specific prenylation. Utilizing GPP as a prenyl donor has not been reported for tryptophan prenyltransferases previously. Both enzymes also catalyzed prenylation of some hydroxynaphthalenes; this has not previously been described for bacterial indole prenyltransferases. Interestingly, SAML0654 transferred prenyl moieties onto the unsubstituted ring of hydroxynaphthalenes.

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Section: Introductionmentioning

confidence: 89%

“…Detailed inspection of the 1 H NMR spectra revealed signals for a regular geranyl residue attached at a C atom. [15] The chemical Acceptance of dihydroxynaphthalenes by 6-DMATS Sa and C-prenylation on the unsubstituted benzene ring…”

Section: Confirmation Of the Prenylation Position Of The Enzyme Productsmentioning

confidence: 99%

Biochemical Investigations of Two 6‐DMATS Enzymes from Streptomyces Reveal New Features of L‐Tryptophan Prenyltransferases

Winkelblech

2014

ChemBioChem

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“…23 Therefore, 1a−9a were incubated with AnaPT in the presence of GPP. HPLC analysis revealed that these compounds were also accepted by AnaPT in the presence of GPP.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Complementary Flavonoid Prenylations by Fungal Indole Prenyltransferases

Zhou

Xie

et al. 2015

J. Nat. Prod.

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Flavonoids are found mainly in plants and exhibit diverse biological and pharmacological activities, which can often be enhanced by prenylations. In plants, such reactions are catalyzed by membrane-bound prenyltransferases. In this study, the prenylation of nine flavonoids from different classes by a soluble fungal prenyltransferase (AnaPT) involved in the biosynthesis of the prenylated indole alkaloid acetylaszonalenin is demonstrated. The behavior of AnaPT toward flavonoids regarding substrate acceptance and prenylation positions clearly differs from that of the indole prenyltransferase 7-DMATS. The two enzymes are therefore complementary in flavonoid prenylations.

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“…Indeed, GPP can be used by AnaPT from N. fischeri for geranylation of (R)-benzodiazepinedione (cyclo-L-Trp-Ant) and five other cyclic dipeptides. C6-and C7-geranylated derivatives were identified as enzyme products (Table 8) (Pockrandt and Li 2013). Obviously, the regioselectivity of the prenyl transfer reaction was reduced in the presence of the long chain donor.…”

Section: Acceptance Of Gpp and Fpp By The Dmats Enzymesmentioning

confidence: 99%

“…It has shown that the double bond The data are adopted from publication for AnaPT (10.1 μM, 6 h) (Zhou et al 2015) The data are adopted from publication for AnaPT (4.0 μM, 16 h) (Pockrandt and Li 2013) n.d. not detected at the ß-position to pyrophosphate is essential for an acceptance by these enzymes. One methyl group can be deleted as in the case of MAPP or shifted to the δ-position as in the case of 2-pentenyl-PP .…”

Section: Acceptance Of Unnatural Dmapp Analogs By the Dmats Enzymesmentioning

confidence: 99%

Impacts and perspectives of prenyltransferases of the DMATS superfamily for use in biotechnology

Fan

Winkelblech

2015

Appl Microbiol Biotechnol

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Prenylated compounds are ubiquitously found in nature and demonstrate interesting biological and pharmacological activities. Prenyltransferases catalyze the attachment of prenyl moieties from different prenyl donors to various acceptors and contribute significantly to the structural and biological diversity of natural products. In the last decade, significant progress has been achieved for the prenyltransferases of the dimethylallyltryptophan synthase (DMATS) superfamily. More than 40 members of these soluble enzymes are identified in microorganisms and characterized biochemically. These enzymes were also successfully used for production of a large number of prenylated derivatives. N1-, C4-, C5-, C6-, and C7-prenylated tryptophan and N1-, C2-, C3-, C4-, and C7-prenylated tryptophan-containing peptides were obtained by using DMATS enzymes as biocatalysts. Tyrosine and xanthone prenyltransferases were used for production of prenylated derivatives of their analogs. More interestingly, the members of the DMATS superfamily demonstrated intriguing substrate and catalytic promiscuity and also used structurally quite different compounds as prenyl acceptors. Prenylated hydroxynaphthalenes, flavonoids, indolocarbazoles, and acylphloroglucinols, which are typical bacterial or plant metabolites, were produced by using several fungal DMATS enzymes. Furthermore, the potential usage of these enzymes was further expanded by using natural or unnatural DMAPP analogs as well as by coexpression with other genes like NRPS and by development of whole cell biocatalyst.

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Geranylation of Cyclic Dipeptides by the Dimethylallyl Transferase AnaPT Resulting in a Shift of Prenylation Position on the Indole Ring

Cited by 19 publications

References 30 publications

Biochemical Investigations of Two 6‐DMATS Enzymes from Streptomyces Reveal New Features of L‐Tryptophan Prenyltransferases

Biochemical Investigations of Two 6‐DMATS Enzymes from Streptomyces Reveal New Features of L‐Tryptophan Prenyltransferases

Complementary Flavonoid Prenylations by Fungal Indole Prenyltransferases

Impacts and perspectives of prenyltransferases of the DMATS superfamily for use in biotechnology

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