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Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities.
Kanis, Fiona C; Broude, Caroline N; Hellwarth, Elle B; Gibbons, William J; Sen, Abhishek K; Adams, Alexandra M; Wang, Xin; Jones, J Andrew.
Afiliación
  • Kanis FC; Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, Ohio, USA.
  • Broude CN; Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, Ohio, USA.
  • Hellwarth EB; Department of Chemistry, Williams College, Williamstown, Massachusetts, USA.
  • Gibbons WJ; Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, Ohio, USA.
  • Sen AK; Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, Ohio, USA.
  • Adams AM; Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, Ohio, USA.
  • Wang X; Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, Ohio, USA.
  • Jones JA; Department of Microbiology, Miami University, Oxford, Ohio, USA.
Biotechnol Prog ; : e3492, 2024 Jun 18.
Article en En | MEDLINE | ID: mdl-38888046
ABSTRACT
N-methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N-dimethyltryptamine (DMT), are gaining interest from the medical community due to their potential as next generation treatments for mental health disorders. The clinical relevance of these compounds has driven scientists to develop biosynthetic production routes to a number of tryptamine drug candidates, and efforts are ongoing to expand and further develop these biosynthetic capabilities. To that end, we have further characterized the substrate preferences of two enzymes involved in tryptamine bio

synthesis:

TrpM, a tryptophan N-methyltransferase from Psilocybe serbica, and PsiD, the gateway decarboxylase of the psilocybin biosynthesis pathway. Here, we show that TrpM can N-methylate the non-native amino acid substrate, 4-hydroxytryptophan, a key intermediate in the Escherichia coli-based recombinant psilocybin biosynthesis pathway. However, the ability to incorporate TrpM into a functional psilocybin biosynthesis pathway was thwarted by PsiD's inability to use N,N-dimethyl-4-hydroxytryptophan as substrate, under the culturing conditions tested, despite demonstrating activity on N-methylated and 4-hydroxylated tryptophan derivatives individually. Taken together, this work expands upon the known substrates for TrpM and PsiD, further increasing the diversity of tryptamine biosynthetic products.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biotechnol Prog Asunto de la revista: BIOTECNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biotechnol Prog Asunto de la revista: BIOTECNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos