Identification of a Cyclosporine-Specific P450 Hydroxylase Gene Through Targeted Cytochrome P450 Complement Disruption in Sebekia Benihana

    Mi-Jin Lee, Hyun-Bum Kim, Yeo Joon Yoon, Koeun Han, Eung-Soo Kim
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    TLDR A gene in Sebekia benihana, CYP-sb21, is needed for a specific reaction on the drug Cyclosporine A, which could be important for hair growth without affecting the immune system.
    The document reports on a study that identified a specific gene, CYP-sb21, in the bacterium Sebekia benihana, which is responsible for the regio-specific hydroxylation of Cyclosporine A (CsA), a process potentially relevant for hair growth without immunosuppression. The researchers sequenced the S. benihana genome, disrupted each of the 21 identified CYP genes, 7 ferredoxins, and 4 ferredoxin reductases, and found that only the mutant lacking CYP-sb21 failed to hydroxylate CsA. This activity was restored by reintroducing the CYP-sb21 gene. Overexpression of CYP-sb21 in S. benihana and a Streptomyces coelicolor mutant increased CsA hydroxylation, suggesting that CYP-sb21 is both necessary and sufficient for this activity. The study also indicated that specific electron transfer proteins are likely involved in the enzyme's activity. This discovery opens up possibilities for biotechnological applications in CsA hydroxylation. The number of people involved in the study was not mentioned as it was a study of bacterial genetics.
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