Zaccaria Marco, Sandlin Natalie, Soen Yoav, Momeni Babak
Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA.
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7670001, Israel.
iScience. 2023 Aug 16;26(9):107632. doi: 10.1016/j.isci.2023.107632. eCollection 2023 Sep 15.
Microbial enzymes can address diverse challenges such as degradation of toxins. However, if the function of interest does not confer a sufficient fitness effect on the producer, the enzymatic function cannot be improved in the host cells by a conventional selection scheme. To overcome this limitation, we propose an alternative scheme, termed "partner-assisted artificial selection" (PAAS), wherein the population of enzyme producers is assisted by function-dependent feedback from an accessory population. Simulations investigating the efficiency of toxin degradation reveal that this strategy supports selection of improved degradation performance, which is robust to stochasticity in the model parameters. We observe that conventional considerations still apply in PAAS: more restrictive bottlenecks lead to stronger selection but add uncertainty. Overall, we offer a guideline for successful implementation of PAAS and highlight its potentials and limitations.
微生物酶可以应对各种挑战,如毒素降解。然而,如果感兴趣的功能对生产者没有足够的适应性影响,那么通过传统的选择方案就无法在宿主细胞中改善酶的功能。为了克服这一限制,我们提出了一种替代方案,称为“伙伴辅助人工选择”(PAAS),其中酶生产者群体由辅助群体的功能依赖性反馈提供帮助。研究毒素降解效率的模拟表明,这种策略有助于选择具有更好降解性能的酶,并且对模型参数的随机性具有鲁棒性。我们观察到,传统的考量在PAAS中仍然适用:更严格的瓶颈会导致更强的选择,但也会增加不确定性。总体而言,我们提供了成功实施PAAS的指导方针,并突出了其潜力和局限性。