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Investigation of Vitamin D₂ and Vitamin D₃ Hydroxylation by Kutzneria albida.

ABSTRACT: The active vitamin D metabolites 25-OH-D and 1α,25-(OH)₂ -D play an essential role in controlling several cellular processes in the human body and are potentially effective in the treatment of several diseases, such as autoimmune diseases, cardiovascular diseases and cancer. The microbial synthesis of vitamin D₂ (VD₂ ) and vitamin D₃ (VD₃ ) metabolites has emerged as a suitable alternative to established complex chemical syntheses. In this study, a novel strain, Kutzneria albida, with the ability to form 25-OH-D₂ and 25-OH-D₃ was identified. To further improve the conversion of the poorly soluble substrates, several solubilizers were tested. 100-fold higher product concentrations of 25-OH-D₃ and tenfold higher concentrations of 25-OH-D₂ after addition of 5 % (w/v) 2-hydroxypropyl β-cyclodextrin (2-HPβCD) were reached. Besides the single-hydroxylation products, the human double-hydroxylation products 1,25-(OH)₂ -D₂ and 1,25-(OH)₂ -D₃ and various other potential single- and double-hydroxylation products were detected. Thus, K. albida represents a promising strain for the biotechnological production of VD₂ and VD₃ metabolites.

SUBMITTER: Schmitz LM

PROVIDER: S-EPMC8359954 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We investigated ecotoxicological effects and toxicogenomic responses in fathead minnows (Pimephales promelas) exposed to an environmentally-relevant concentration (0.83 mg/L) of the munitions compound cyclotrimethylenetrinitramine (RDX) in one year and multi-generational assays. In the one year assay, RDX effects were discerned by comparing breeding groups reared in control or RDX-exposure conditions for one year. RDX had no detectable effect on gonad-somatic index, or condition factor in females assayed at 1 day and at 1, 3, 6, 9, and 12 months, however the liver-somatic index was significantly increased versus controls only at the 12 month time point. RDX had no effect on live-prey capture rates at all time points assayed and no significant impacts on egg production, fertilization or hatch success in the 1-year exposure trial. Genomic analyses indicated that RDX exposure caused limited differential expression of transcripts within time points and no functional conservation of effects indicative of RDX exposure among time points for either brain or liver tissues in the one year exposure. In the multi-generational assay, the effects of acute (96h) exposure to RDX were compared in fish reared to the F2 generation in either control or RDX-exposure conditions. The RDX-reared fish were not observed to have appreciably enhanced RDX tolerance versus the control-reared fish. However, significant differences in gene expression were observed among the control and RDX-reared fish related to neuro-excitatory glutamate metabolism, sensory signaling and processes in neurological development. In total, our results indicate that exposure to an RDX concentration approximating maximum levels observed in the field (0.83 mg/L) caused limited impacts in fathead minnows in a one year exposure, however caused altered expression in genes involved in neural function in a multi-generational exposure. P. promelas larvae produced in the original one year exposure were collected and grown out to sexual maturity while being maintained in the same treatment (control or 0.83 mg/L RDX) as their respective F0 parental generation. Once the fish reached sexual maturity, they were placed into eight experimental units for both control and RDX treatment consisting of four females and two males and were maintained with the same experimental conditions as the F0 generation. To determine if the chronic, multi-generational exposure to RDX resulted in any change in sensitivity to RDX, 90 dph progeny (F2 or sub-adults) of the control and RDX-exposed F1 generation were subjected to a challenge experiment where the fish were exposed to RDX at 5 mg/L.

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Investigation of Vitamin D2 and Vitamin D3 Hydroxylation by Kutzneria albida.

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Investigation of Vitamin D₂ and Vitamin D₃ Hydroxylation by Kutzneria albida.