Department of Biochemistry, University of Cambridge, Cambridge, UK.
Department of Biomedical & Biotechnological Sciences, University of Catania, Catania, Italy.
Nat Commun. 2024 Oct 31;15(1):9076. doi: 10.1038/s41467-024-52816-2.
Construction of minimal metabolic networks (MMNs) contributes both to our understanding of the origins of metabolism and to the efficiency of biotechnological processes by preventing the diversion of flux away from product formation. We have designed MMNs using a novel in silico synthetic biology pipeline that removes genes encoding enzymes and transporters from genome-scale metabolic models. The resulting minimal gene-set still ensures both viability and high growth rates. The composition of these MMNs has defined a new functional class of genes termed Network Efficiency Determinants (NEDs). These genes, whilst not essential, are very rarely eliminated in constructing an MMN, suggesting that it is difficult for metabolism to be re-routed to obviate the need for such genes. Moreover, the removal of NED genes from an MMN significantly reduces its global efficiency. Bioinformatic analyses of the NED genes have revealed that not only do these genes have more genetic interactions than the bulk of metabolic genes but their protein products also show more protein-protein interactions. In yeast, NED genes are predominantly single-copy and are highly conserved across evolutionarily distant organisms. These features confirm the importance of the NED genes to the metabolic network, including why they are so rarely excluded during minimisation.
构建最小代谢网络（MMNs）有助于我们理解代谢的起源，并通过防止通量从产物形成中分流来提高生物技术过程的效率。我们使用一种新颖的计算合成生物学管道，从基因组规模的代谢模型中去除编码酶和转运蛋白的基因，设计了 MMNs。由此产生的最小基因集仍然确保了生存能力和高生长速率。这些 MMNs 的组成定义了一类新的功能基因，称为网络效率决定因素（NEDs）。这些基因虽然不是必需的，但在构建 MMN 时很少被消除，这表明代谢很难被重新路由以避免对这些基因的需求。此外，从 MMN 中去除 NED 基因会显著降低其全局效率。对 NED 基因的生物信息学分析表明，这些基因不仅比大多数代谢基因具有更多的遗传相互作用，而且其蛋白质产物也显示出更多的蛋白质-蛋白质相互作用。在酵母中，NED 基因主要是单拷贝的，并且在进化上相距很远的生物中高度保守。这些特征证实了 NED 基因对代谢网络的重要性，包括为什么在最小化过程中很少排除它们。
