141979-69-3Relevant academic research and scientific papers
METHODS FOR PRODUCING D-TRYPTOPHAN AND SUBSTITUTED D-TRYPTOPHANS
-
Page/Page column 17-18, (2021/04/01)
Single-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carboxylic acids in both primary and secondary metabolism; and are of great interest due to their biocatalytic potentials. The single-module NRPS IvoA is essential for fungal pigment biosynthesis. As disclosed herein, we show that IvoA catalyzes ATP-dependent unidirectional stereoinversion of L-tryptophan to D-tryptophan with complete conversion. While the stereoinversion is catalyzed by the epimerization (E) domain, the terminal condensation (C) domain stereoselectively hydrolyzes D-tryptophanyl-S-phosphopantetheine thioester and thus represents a noncanonical C domain function. Using IvoA, we demonstrate a biocatalytic stereoinversion/deracemization route to access a variety of substituted D-tryptophan analogs in high enantiomeric excess.
Synthesis method of indole monosubstituted 2-hydroxy-3-(1H-indole-3-yl) propionic acid compound
-
Paragraph 0038-0046, (2020/07/15)
The invention relates to a synthesis method of an indole monosubstituted 2-hydroxy-3-(1H-indole-3-yl) propionic acid compound, which comprises the following steps of (1) reacting a compound shown as aformula I, DL-serine and acetic anhydride in the presence of a solvent under the protection of inert gas, removing the solvent, and carrying out heat treatment under alkaline conditions to obtain a compound shown as a formula II, (2) under the protection of inert gas, enabling the compound shown in a formula II to react in the presence of nitrite, H2SO4 and water to prepare a compound shown in aformula III, the structural formula of the compound in the formula I being shown in the specification, the structural formula of the compound in the formula II being shown in the specification, the structural formula of the compound in the formula III being shown in the specifications, and in the formulas I, II and III, R being one of alkyl, alkoxy and halogen. Monosubstituted indole and serine are used as raw materials, the indole monosubstituted 2-hydroxy-3-(1H-indole-3-yl) propionic acid compound is prepared through a chemical synthesis method, the raw materials are easy to obtain and cheap, operation is easy, few steps are needed, and the product yield is high.
Complete Stereoinversion of l -Tryptophan by a Fungal Single-Module Nonribosomal Peptide Synthetase
Hai, Yang,Jenner, Matthew,Tang, Yi
supporting information, p. 16222 - 16226 (2019/10/14)
Single-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carboxylic acids in both primary and secondary metabolism and are of great interest due to their biocatalytic potentials. The single-module NRPS IvoA is essential for fungal pigment biosynthesis. Here, we show that IvoA catalyzes ATP-dependent unidirectional stereoinversion of l-tryptophan to d-tryptophan with complete conversion. While the stereoinversion is catalyzed by the epimerization (E) domain, the terminal condensation (C) domain stereoselectively hydrolyzes d-tryptophanyl-S-phosphopantetheine thioester and thus represents a noncanonical C domain function. Using IvoA, we demonstrate a biocatalytic stereoinversion/deracemization route to access a variety of substituted d-tryptophan analogs in high enantiomeric excess.
One-Pot Biocatalytic Synthesis of Substituted d -Tryptophans from Indoles Enabled by an Engineered Aminotransferase
Parmeggiani, Fabio,Rué Casamajo, Arnau,Walton, Curtis J. W.,Galman, James L.,Turner, Nicholas J.,Chica, Roberto A.
, p. 3482 - 3486 (2019/04/13)
d-Tryptophan and its derivatives are important precursors of a wide range of indole-containing pharmaceuticals and natural products. Here, we developed a one-pot biocatalytic process enabling the synthesis of d-tryptophans from indoles in good yields and high enantiomeric excess (91% to >99%). Our method couples the synthesis of l-tryptophans catalyzed by Salmonella enterica tryptophan synthase with a stereoinversion cascade mediated by Proteus myxofaciens l-amino acid deaminase and an aminotransferase variant that we engineered to display native-like activity toward d-tryptophan. Our process is applicable to preparative-scale synthesis of a broad range of d-tryptophan derivatives containing electron-donating or -withdrawing substituents at all benzene-ring positions on the indole group.
De novo Biosynthesis of “Non-Natural” Thaxtomin Phytotoxins
Winn, Michael,Francis, Daniel,Micklefield, Jason
supporting information, p. 6830 - 6833 (2018/06/04)
Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to “non-natural” product target compounds.
Multisite prenylation of 4-substituted tryptophans by dimethylallyltryptophan synthase
Rudolf, Jeffrey D.,Wang, Hong,Poulter, C. Dale
, p. 1895 - 1902 (2013/04/23)
The aromatic prenyltransferase dimethylallyltryptophan synthase in Claviceps purpurea catalyzes the normal prenylation of tryptophan at C4 of the indole nucleus in the first committed step of ergot alkaloid biosynthesis. 4-Methyltryptophan is a competitive inhibitor of the enzyme that has been used in kinetic studies. Upon investigation of background activity during incubations of 4-methyltryptophan with dimethylallyl diphosphate, we found that the analogue was an alternate substrate, which gave four products. The structures of three of these compounds were established by 1H NMR and 2D NMR studies and revealed that dimethylallyltryptophan synthase catalyzed both normal and reverse prenylation at C3 of the indole ring and normal prenylation of N1. Similarly, 4-methoxytryptophan was an alternate substrate, giving normal prenylation at C5 as the major product. 4-Aminotryptophan, another alternate substrate, gave normal prenylation at C5 and C7. The ability of dimethylallyltryptophan synthase to prenylate at five different sites on the indole nucleus, with normal and reverse prenylation at one of the sites, is consistent with a dissociative electrophilic alkylation of the indole ring, where orientation of the substrates within the active site and substituent electronic effects determine the position and type of prenylation. These results suggest a common mechanism for prenylation of tryptophan by all of the members of the structurally related dimethylallyltryptophan synthase family.
Synthesis of enantiomerically pure 4-alkylsubstituted tryptophan derivatives by a combination of organometallic reactions with enantioselective enzymatic transformations
Nettekoven, Matthias,Psiorz, Manfred,Waldmann, Herbert
, p. 1425 - 1428 (2007/10/02)
The synthesis of enantiomerically pure 4-substituted tryptophans 12 is described. Key steps are i) the introduction of an alkyl substituent into the 4-position of the indole via regioselective lithiation of N-TIPS protected gramine and ii) the enantioselective saponification of the phenyl acetamides of 4-substituted tryptophans by the enzyme penicillin G acylase.
