Filamentous fungi comprise an abundance of gene clusters that encode high-value metabolites, whereas affluent gene clusters remain silent during laboratory conditions. Complex cellular metabolism further limits these metabolite yields. Therefore, diverse strategies such as genetic engineering and chemical mutagenesis have been developed to activate these cryptic pathways and improve metabolite productivity. However, lower efficiencies of gene modifications and screen tools delayed the above processes. To address the above issues, this review describes an alternative design-construction evaluation optimization (DCEO) approach. The DCEO tool provides theoretical and practical principles to identify potential pathways, modify endogenous pathways, integrate exogenous pathways, and exploit novel pathways for their diverse metabolites and desirable productivities. This DCEO method also offers different tactics to balance the cellular metabolisms, facilitate the genetic engineering, and exploit the scalable metabolites in filamentous fungi.

中文翻译：

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丝状真菌代谢物探索的高级策略。

丝状真菌包含大量编码高价值代谢产物的基因簇，而富裕的基因簇在实验室条件下保持沉默。复杂的细胞代谢进一步限制了这些代谢产物的产量。因此，已开发出多种策略，例如基因工程和化学诱变，以激活这些隐秘途径并提高代谢产物的生产率。但是，基因修饰和筛选工具的效率较低，延迟了上述过程。为了解决上述问题，本次综述介绍了一种替代的设计－构造评估优化（DCEO）方法。DCEO工具提供了理论和实践原则，以识别潜在途径，修改内源性途径，整合外源性途径，并开发出新颖的途径来实现其多样化的代谢产物和理想的生产率。这种DCEO方法还提供了不同的策略来平衡细胞代谢，促进基因工程以及利用丝状真菌中可扩展的代谢产物。