Microbial production of many lipophilic compounds is often limited by product toxicity to host cells. Engineering cell walls can help mitigate the damage caused by lipophilic compounds by increasing tolerance to those compounds. To determine if the cell wall engineering would be effective in enhancing lipophilic compound production, we used a previously constructed squalene-overproducing yeast strain (SQ) that produces over 600 mg/L of squalene, a model membrane-damaging lipophilic compound. This SQ strain had significantly decreased membrane rigidity, leading to increased cell lysis during fermentation. The SQ strain was engineered to restore membrane rigidity by activating the cell wall integrity (CWI) pathway, thereby further enhancing its squalene production efficiency. Maintenance of CWI was associated with improved squalene production, as shown by cell wall remodeling through regulation of Ecm33, a key regulator of the CWI pathway. Deletion of ECM33 in the SQ strain helped restore membrane rigidity and improve stress tolerance. Moreover, ECM33 deletion suppressed cell lysis and increased squalene production by approximately 12% compared to that by the parent SQ strain. Thus, this study shows that engineering of the yeast cell wall is a promising strategy for enhancing the physiological functions of industrial strains for production of lipophilic compounds.

中文翻译：

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工程细胞壁完整性可提高酵母中角鲨烯的产量。

许多亲脂性化合物的微生物产生通常受到产物对宿主细胞毒性的限制。通过增加对亲脂性化合物的耐受性，工程细胞壁可以帮助减轻由亲脂性化合物引起的损害。为了确定细胞壁工程改造是否有效提高亲脂性化合物的产量，我们使用了先前构建的鲨烯过量生产酵母菌株（SQ），该菌株可产生超过600 mg / L的鲨烯，这是一种破坏膜的亲脂性化合物模型。该SQ菌株具有显着降低的膜刚性，导致发酵过程中细胞裂解增加。通过激活细胞壁完整性（CWI）途径，工程SQ菌株可恢复膜的刚性，从而进一步提高其鲨烯的生产效率。维持CWI与改善角鲨烯产量有关，如通过Ccm通路的关键调节因子Ecm33的调节引起的细胞壁重塑所示。SQ菌株中ECM33的缺失有助于恢复膜的刚性并改善应力耐受性。而且，与亲本SQ菌株相比，ECM33缺失抑制细胞裂解并使角鲨烯产生增加约12％。因此，这项研究表明，对酵母细胞壁进行改造是增强工业菌株生产亲脂性化合物的生理功能的有前途的策略。与亲本SQ菌株相比，ECM33缺失抑制了细胞裂解，并使角鲨烯产量提高了约12％。因此，这项研究表明，对酵母细胞壁进行改造是增强工业菌株生产亲脂性化合物的生理功能的有前途的策略。与亲本SQ菌株相比，ECM33缺失抑制了细胞裂解，并使角鲨烯产量提高了约12％。因此，这项研究表明，对酵母细胞壁进行改造是增强工业菌株生产亲脂性化合物的生理功能的有前途的策略。