Ketimine reductase/CRYM catalyzes reductive alkylamination of α-keto acids, confirming its function as an imine reductase

Hallen, André; Cooper, Arthur J. L.; Smith, Jason Scott; Jamie, Joanne F.; Karuso, Peter

doi:10.1007/s00726-015-2044-8

Cited by 14 publications

(19 citation statements)

References 19 publications

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“…Furthermore, CRYM expression is possibly upregulated through the activator protein-1 (AP-1) site in the promoter (37). Another important CRYM function has also been identified: When combined with ketimine reductase, it may act as a classical imine reductase (38). In addition, CRYM has a critical role and is regarded as a novel androgen-regulated gene whose expression is elevated in prostate cancer (39).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation in CRYM in a Chinese family with hearing loss using whole‑exome sequencing

Min

Deng

et al. 2020

Exp Ther Med

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Previous studies have identified ~50 genes that contribute to non-syndromic autosomal dominant sensorineural deafness (DFNA). However, in numerous families with hearing loss, the specific gene mutation remains to be identified. In the present study, the clinical characteristics and gene mutations were analyzed in a Chinese pedigree with hereditary hearing loss. The clinical characteristics of the family members were assessed and a detailed audiology function examination was performed. Whole-exome sequencing (WES) was performed to identify the gene mutation responsible for the hearing loss. Sanger sequencing was used to verify the candidate mutation detected in the family. The family consisted of 31 members, seven of whom were diagnosed with sensorineural deafness of varying degrees. No mutation was identified by the general deafness gene chip. However, a novel heterozygous mutation in exon 3 (c.152C>T; Pro51Leu) of the gene crystallin µ (CRYM) was identified by WES. This result was further verified by Sanger sequencing. Co-segregation of genotypes and phenotypes suggested that this novel mutation was instrumental for the hearing loss/DFNA. In conclusion, the present study identified a novel pathogenic mutation, NM_001888.5(CRYM): c.152C>T(Pro51Leu), associated with DFNA. This mutation has not been reported previously and further functional studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation in CRYM in a Chinese family with hearing loss using whole‑exome sequencing

Min

Deng

et al. 2020

Exp Ther Med

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“…Combining in vitro assays with the ALD1 and SARD4 homologs from H. serrata with use of deuterium‐labeled l ‐lysine indicated that SARD4 reduces the ketiminic C=N bond of 1,2‐DP rather than the C=C bond of the 2,3‐DP enamine (Xu et al ., ). This is in line with the reported reduction of ketimine substrates by mammalian CRYM (Hallen et al ., ). SARD4‐mediated reductive consumption of 1,2‐DP might shift the ketimine/enamine equilibrium towards the ketimine form and thus constantly reestablish reducible 1,2‐DP from the chemically more stable enamine 2,3‐DP.…”

Section: Catabolism Of L‐lysine To Pip and Conversion Of Pip To N‐hymentioning

confidence: 97%

l‐lysine metabolism to N‐hydroxypipecolic acid: an integral immune‐activating pathway in plants

Hartmann

Zeier

2018

The Plant Journal

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l-lysine catabolic routes in plants include the saccharopine pathway to α-aminoadipate and decarboxylation of lysine to cadaverine. The current review will cover a third l-lysine metabolic pathway having a major role in plant systemic acquired resistance (SAR) to pathogen infection that was recently discovered in Arabidopsis thaliana. In this pathway, the aminotransferase AGD2-like defense response protein (ALD1) α-transaminates l-lysine and generates cyclic dehydropipecolic (DP) intermediates that are subsequently reduced to pipecolic acid (Pip) by the reductase SAR-deficient 4 (SARD4). l-pipecolic acid, which occurs ubiquitously in the plant kingdom, is further N-hydroxylated to the systemic acquired resistance (SAR)-activating metabolite N-hydroxypipecolic acid (NHP) by flavin-dependent monooxygenase1 (FMO1). N-hydroxypipecolic acid induces the expression of a set of major plant immune genes to enhance defense readiness, amplifies resistance responses, acts synergistically with the defense hormone salicylic acid, promotes the hypersensitive cell death response and primes plants for effective immune mobilization in cases of future pathogen challenge. This pathogen-inducible NHP biosynthetic pathway is activated at the transcriptional level and involves feedback amplification. Apart from FMO1, some cytochrome P450 monooxygenases involved in secondary metabolism catalyze N-hydroxylation reactions in plants. In specific taxa, pipecolic acid might also serve as a precursor in the biosynthesis of specialized natural products, leading to C-hydroxylated and otherwise modified piperidine derivatives, including indolizidine alkaloids. Finally, we show that NHP is glycosylated in Arabidopsis to form a hexose-conjugate, and then discuss open questions in Pip/NHP-related research.

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“…or any other IRED homologs which have been reported [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] . The CpIM1 gene was identified using a human Mu crystallin (CRYM) gene sequence as a template, which is reportedly a ketimine reductase that catalyzes the alkylamination of various keto-acids [37] . CpIM1 showed a 24.5% identity with the human CRYM gene and belonged to the ornithine cyclodeaminase (OCD-Mu) family of proteins.…”

Section: Resultsmentioning

confidence: 99%

Imine reduction by an Ornithine cyclodeaminase/μ-crystallin homolog purified from Candida parapsilosis ATCC 7330

Mahesh¹,

Chadha²

2021

Biotechnology Reports

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Highlights Novel imine reductase from yeast Candida parapsilosis purified and characterized. CpIM1 belongs to unexplored Ornithine cyclodeaminase/Mu crystallin protein family CpIM1 catalyzed stereospecific alkylamination of α-ketoacids/ketoesters. CpIM1 also reduced cyclic and aryl imines. First report on enzymatic alkylamination of α-ketoesters and reduction of arylimines.

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Ketimine reductase/CRYM catalyzes reductive alkylamination of α-keto acids, confirming its function as an imine reductase

Cited by 14 publications

References 19 publications

Identification of a novel mutation in CRYM in a Chinese family with hearing loss using whole‑exome sequencing

Identification of a novel mutation in CRYM in a Chinese family with hearing loss using whole‑exome sequencing

l‐lysine metabolism to N‐hydroxypipecolic acid: an integral immune‐activating pathway in plants

Imine reduction by an Ornithine cyclodeaminase/μ-crystallin homolog purified from Candida parapsilosis ATCC 7330

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