Tetrandrine is the most effective small molecule that has been found to inhibit the Ebola virus. It is a typical bisbenzylisoquinoline alkaloid and is the main active ingredient in Stephania tetrandra. Metabolic engineering and synthetic biology are potential methods for efficient and rapid acquisition of tetrandrine. S-adenosyl-L-methionine: (S)-norcoclaurine-6-O-methyltransferase (6OMT) is a rate-limiting step involved in the biosynthesis of tetrandrine. In this study, we identify S-adenosyl-L-methionine: (S)-norcoclaurine-6-O-methyltransferase from S. tetrandra, which catalyzes the conversion of (S)-norcoclaurine to (S)-coclaurine. Four 6OMT-like genes were cloned from S. tetrandra. An in vitro enzyme assay showed that St6OMT1 could catalyze the conversion of (S)-norcoclaurine to produce (S)-coclaurine. St6OMT2 can catalyze the production of very few (S)-coclaurine molecules, accompanied by more by-products with m/z 300, compared to St6OMT1. The newly discovered 6OMTs will provide an optional genetic component for benzylisoquinoline alkaloid (BIA) synthetic biology research. This work will lay the foundation for the analysis of the biosynthetic pathway of tetrandrine in S. tetrandra.

中文翻译：

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O-甲基转移酶的表征参与了粉防己的粉防己碱的生物合成

粉防己碱是已发现可抑制埃博拉病毒的最有效的小分子。它是一种典型的双苄基异喹啉生物碱，是黄芪中的主要活性成分。代谢工程和合成生物学是有效和快速获取粉防己碱的潜在方法。S-腺苷-L-甲硫氨酸：(S)-norcoclaurine-6-O-methyltransferase (6OMT) 是参与粉防己碱生物合成的限速步骤。在这项研究中，我们鉴定了 S-腺苷-L-甲硫氨酸：来自防毒粉虱的 (S)-norcoclaurine-6-O-methyltransferase，它催化 (S)-norcoclaurine 转化为 (S)-coclaurine。四个 6OMT 样基因是从 S. tandra 中克隆的。体外酶分析表明，St6OMT1 可以催化 (S)-norcoclaurine 转化为 (S)-coclaurine。与 St6OMT1 相比，St6OMT2 可以催化产生很少的 (S)-coclaurine 分子，伴随有更多 m/z 300 的副产物。新发现的 6OMT 将为苄基异喹啉生物碱 (BIA) 合成生物学研究提供可选的遗传成分。该工作将为分析粉防己碱的生物合成途径奠定基础。