For many secondary metabolites, heterologous synthesis is the definitive step to determine their required biosynthetic genes. Using a multivector expression system in Saccharomyces cerevisiae, we reconstituted not only two natural statins from two fungal species, i.e., lovastatin from Aspergillus terreus and FR901512 from Xylaria grammica, but also new statin structures by mixing their genes. Combinatorial gene exchange experiments revealed the functional promiscuity of two polyketide synthases in A. terreus, lovB, and lovF; they could synthesize FR901512 with Xylaria genes. Key structure determinants of statins are essential accessory genes that are irreplaceable across species.

中文翻译：

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木霉和曲霉的异源基因组合合成新型他汀类药物

对于许多次级代谢产物而言，异源合成是确定其所需生物合成基因的决定性步骤。使用酿酒酵母中的多载体表达系统，我们不仅重构了来自两种真菌物种的两种天然他汀类药物，即来自曲霉的洛伐他汀和来自Xylaria grammica的FR901512 ，而且还通过混合它们的基因来重构了新的他汀类结构。组合基因交换实验揭示了A. terreus，lovB和lovF中两种聚酮合酶的功能混杂; 他们可以用Xylaria合成FR901512基因。他汀类药物的关键结构决定因素是跨物种不可替代的重要辅助基因。