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Results for “prenyltransferase gene”

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PubMed2025

The telomere-to-telomere genome of Sanicula chinensis unveils genetic underpinnings of low furanocoumarin diversity and content in one basal lineage of Apiaceae.

Furanocoumarins are specialized defense compounds in Apiaceae, but the evolutionary path of their biosynthesis is not well understood. We generated a telomere-to-telomere (T2T) genome for Sanicula chinensis, an early-diverging species within the Saniculoideae subfamily, to explore its evolution. Comparative genomics revealed that S. chinensis and Apioideae species each underwent unique whole-genome duplication (WGD). Unlike most species in the Apioideae subfamily, S. chinensis produces a limited diversity and content of furanocoumarins but shows high esculetin levels. This metabolic profile likely stems from three genetic factors: elevated expression of p-Coumaroyl ester 3'-hydroxylase (C3'H) and hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT), which shift the metabolic pathway toward simple coumarins; the absence of a key biosynthetic gene cluster, including prenyltransferase (PT) and p-coumaroyl-CoA 2'-hydroxylase (C2'H), found in Apioideae; and incomplete or inactive PT enzymes in S. chinensis. Our results not only shed light on the evolutionary history of furanocoumarin biosynthesis in Apiaceae, but also provide avenues for tailoring furanocoumarin content for agricultural or medical applications in plants.

Furocoumarins↗

PubMed2025

Gene amir_2071 of Actinosynnema mirum DSM 43827 encodes a dimethylallyltryptophan synthase superfamily protein responsible for the production of prenylated tyrosine.

Actinosynnema mirum DSM 43827 is a bacterium from the small genus Actinosynnema within the rapidly growing actinomycete family Pseudonocardiaceae (Land M et al. Stand Genomic Sci 1:46-53 2009). Despite its diverse repertoire of specialized metabolite biosynthetic gene clusters (BGCs), the potential of A. mirum for production of bioactive molecules is not fully explored. Here, we used a heterologous expression approach to gain deeper insight into this issue. In this work we report that expression of in silico predicted BGC#4 from A. mirum in S. albus Del14 and S. lividans ΔYA9 led to production of several prenylated derivatives of tyrosine. Their most likely structures, according to MS and MS/MS data, agreed with 4-O-prenyl-(L)-tyrosine and its N-acetyl derivative, previously described in lichen-forming fungi (Iacovelli R et al. J Nat Prod 87:2243-2254 2024). Further experiments confirm the production of the aforementioned compounds is governed by a single structural gene, amir_2071 for prenyltransferase of dimethylallyltryptophan synthase (DMATS) superfamily, whose homologs are abundant in bacterial genomes.

Tyrosine↗

PubMed2026

Mice with the mono-allelic p.R37H Dhdds variant show aberrant glycosylation and interneuron deficits.

Developmental delay and seizures with or without movement abnormalities (OMIM 617836) caused by heterozygous pathogenic variants in the DHDDS gene (DHDDS-CDG) is a rare genetic disease that belongs to the progressive encephalopathy spectrum. It results in cognitive delay in affected children, accompanied by myoclonus, seizures, ataxia and tremor, which worsens over time. DHDDS encodes a subunit of a DHDDS/NUS1 cis-prenyltransferase (cis-PTase), a branch point enzyme of the mevalonate pathway essential for N-linked glycosylation. We describe the first mouse model of this disease, DhddsR37H+/- strain, heterozygous for the human recurrent de novo c.110G>A:p.R37H pathogenic variant. DhddsR37H+/- mice present with seizures, myoclonus and memory deficits associated with reduced density or/and maturity of inhibitory interneurons in the cortex. Multiomics analyses of mouse CNS tissues, together with the enzymatic/structural characterization of the R37H DHDDS mutant protein, reveal that the variant produces a catalytically inactive enzyme and results in a brain dolichol deficit, aberrant glycosylation of brain glycoproteins, including those involved in synaptic transmission and major perturbations in the CNS proteome and lipidome. Acetazolamide, a carbonic anhydrase inhibitor clinically approved for treatment of glaucoma, epilepsy, and intracranial hypertension, and successfully used "off-label" to treat genetic movement disorders, reduces seizure susceptibility to pentylenetetrazol in DhddsR37H+/- mice, suggesting potential therapeutic value of using this drug in human DHDDS-CDG patients. Together, our results define cis-PTase as a master regulator of CNS development and function and establish that its monoallelic debilitating variants cause a novel congenital disorder of glycosylation associated with aberrant levels of neuronal proteins and lipids.

DHDDS↗