Resource-aware whole-cell model of division of labour in a microbial consortium for complex-substrate degradation.
Resource-aware whole-cell model of division of labour in a microbial consortium for complex-substrate degradation.
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DOI：
10.1186/s12934-022-01842-0
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发表时间：
2022-06-14
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
低成本可持续原料对于商业上可行的生物技术至关重要。这些原料通常来自植物或食物垃圾，含有多种不同的复杂生物分子，需要多种酶才能水解和代谢。当前的标准生物技术使用单一培养物，其中单个宿主表达综合生物过程所需的所有蛋白质。然而，这些宿主在生长受到影响之前表达蛋白质的能力有限。这种限制可以通过利用联合体中的劳动分工 (DOL) 来克服，其中每个成员表达较长降解途径的单一蛋白质。在这里，我们模拟了一个双菌株联合体，其中一种菌株表达内切水解酶，另一种菌株表达外切水解酶，以协同降解复杂的底物。我们的结果表明，增加表达以增强降解与较高表达造成的负担之间存在平衡。一旦达到负担阈值，该联盟将始终比同等的单细胞单一培养表现更好。我们证明，资源感知全细胞模型可用于预测使用联盟系统克服负担的好处和局限性。我们的模型预测了 DOL 有利于淀粉生长的表达区域，这将有助于为此以及其他复杂底物降解途径做出明智的设计选择。在线版本包含可在 10.1186/s12934-022-01842-0 获取的补充材料。
Low-cost sustainable feedstocks are essential for commercially viable biotechnologies. These feedstocks, often derived from plant or food waste, contain a multitude of different complex biomolecules which require multiple enzymes to hydrolyse and metabolise. Current standard biotechnology uses monocultures in which a single host expresses all the proteins required for the consolidated bioprocess. However, these hosts have limited capacity for expressing proteins before growth is impacted. This limitation may be overcome by utilising division of labour (DOL) in a consortium, where each member expresses a single protein of a longer degradation pathway. Here, we model a two-strain consortium, with one strain expressing an endohydrolase and a second strain expressing an exohydrolase, for cooperative degradation of a complex substrate. Our results suggest that there is a balance between increasing expression to enhance degradation versus the burden that higher expression causes. Once a threshold of burden is reached, the consortium will consistently perform better than an equivalent single-cell monoculture. We demonstrate that resource-aware whole-cell models can be used to predict the benefits and limitations of using consortia systems to overcome burden. Our model predicts the region of expression where DOL would be beneficial for growth on starch, which will assist in making informed design choices for this, and other, complex-substrate degradation pathways. The online version contains supplementary material available at 10.1186/s12934-022-01842-0.
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影响因子：
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