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NET works after all? Engineering robustness through diversity

机译：NET到底能用吗？通过多样性实现工程鲁棒性

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Classical Thermodynamics restricts engineering. These restrictions are independent of mechanism and kinetics, and thereby inescapable. Forgetting these restrictions can lead to over-optimistic designs for making bio-plastics from waste, and to erroneous ideas on early or new Life on this or other planets. This can be rectified by putting the thermodynamics in place. Is every biochemical network design feasible, provided one puts classical thermodynamics in place? Or, are there other, ill-recognized, generic restrictions to bioengineering?For a while a Non-Equilibrium Thermodynamics (NET) has been trying to discover behaviors of dynamical systems away from equilibrium that are completely independent of kinetics and mechanism and thereby not engineerable. The principles discovered were of limited use to bioengineering however.We here show that processes away from equilibrium must indeed depend on kinetics and mechanism, but, importantly, not on all kinetic and mechanistic details: There are limitations to what the engineering of mechanisms and kinetics can achieve. It is of course better to recognize what is impossible before trying to engineer the impossible. Importantly, the new NET methodology also shows that system properties that are possible, can be engineered only in certain ways.The new NET methodology also enables to understand, and perhaps engineer towards, a performance that, by adjusting the network, remains optimal when conditions are changing. Using our in silico discovery tool, we show that this may indeed occur in the ArcheonS. solfataricus. What we call ‘variomatic’ gear shifting is a way that some cells may use to self-engineer their ways to maximal growth rates in environments that lack robust resources, such as in environments with fluctuating oxygen levels.Population heterogeneity is another mechanism that can increase the robustness of a cell factory. We discuss a NET principle that suggests ways in which one can engineer the cells’ diversity. Transcription burst size rather than kinetics should be modulated for making a diverse population perform much better than its average.
机译：经典的热力学限制了工程。这些限制与机理和动力学无关，因此不可避免。忘记这些限制会导致从废物中制备生物塑料的设计过于乐观，并导致在这个星球或其他星球上的早期或新生命中出现错误的想法。可以通过放置热力学来解决此问题。只要将经典的热力学放在适当的位置，每个生化网络的设计是否可行？还是有其他未经认可的生物工程通用限制？一段时间以来，非平衡热力学（NET）一直在试图发现动力学系统的行为偏离平衡，而该行为完全独立于动力学和机理，因此无法进行工程设计。然而，发现的原理在生物工程学中的应用有限。我们在这里表明，远离平衡的过程确实必须取决于动力学和机理，但重要的是，并非取决于所有动力学和机理的细节：对机理和动力学的工程学存在局限性可以实现。当然，最好在尝试设计不可能的事物之前先认识到不可能的事物。重要的是，新的NET方法还表明只能通过某些方式对可能的系统属性进行工程设计。新的NET方法还可以通过调整网络来理解并为之设计性能，该性能可以通过调整网络在特定条件下保持最佳状态正在改变。使用我们的计算机模拟发现工具，我们证明了这确实可能在ArcheonS中发生。 solfataricus。我们称之为``可变''变速的一种方式，一些细胞可以在缺乏强大资源的环境中（例如在氧气水平波动的环境中）自我工程化以实现最大增长率。电池工厂的坚固性。我们讨论了一种NET原理，该原理提出了一种可以设计细胞多样性的方法。应当调节转录爆发的大小而不是动力学，以使多样化的人群表现好于其平均值。

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