Different natural aromatic/heterocyclic L-amino acids were biotransformed into aryl/heteroaryl ethanol metabolites via oxidative deamination, decarboxylation and reduction cascades using live baker's yeast cells producing intracellular human CYP2D6 enzyme. Among the three yeast strains expressing 3 different CYP2D6 variants, CYP2D6(2) (i.e. CYP2D6 wild-type) provided the best result under neutral pH conditions at RT. We have successfully converted six natural amino acids into their corresponding alcohols, having one carbon atom less, with moderate yields. Some of the downstream products like tryptophol and tyrosol induced the pTrKB (Tropomyosin receptor kinase B) activation pattern similar to that of BDNF (brain-derived neurotrophic factor), thereby depicting potential antidepressant activity. Control experiments and molecular modelling studies revealed that this tandem bio-transformation probably happens via a pyruvate intermediate. This study establishes that CYP2D6-expressing live yeast cells can be a powerful tool for the enzymatic C–N, C–C bond cleavage of amino-acids.

中文翻译：

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使用表达人 CYP2D6 的活面包酵母将氨基酸转化为芳基/杂芳基乙醇代谢物

使用产生细胞内人 CYP2D6 酶的活面包酵母细胞，通过氧化脱氨、脱羧和还原级联，将不同的天然芳香族/杂环L -氨基酸生物转化为芳基/杂芳基乙醇代谢物。在表达 3 种不同 CYP2D6 变体的三种酵母菌株中，CYP2D6(2)（即CYP2D6 野生型）在 RT 中性 pH 条件下提供了最佳结果。我们已经成功地将六种天然氨基酸转化为相应的醇，少一个碳原子，且产率适中。一些下游产品，如色氨酸和酪醇，诱导 pTrKB（原肌球蛋白受体激酶 B）激活模式，类似于 BDNF（脑源性神经营养因子），从而展现出潜在的抗抑郁活性。对照实验和分子模型研究表明，这种串联生物转化可能通过丙酮酸中间体发生。这项研究表明，表达 CYP2D6 的活酵母细胞可以成为酶促氨基酸 C-N、C-C 键裂解的强大工具。