Enzyme promiscuity shapes adaptation to novel growth substrates
Enzyme promiscuity shapes adaptation to novel growth substrates
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DOI：
10.15252/msb.20188462
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发表时间：
2019-04-01
影响因子：
9.9
通讯作者：
Feist, Adam M.
中科院分区：
文献类型：
--
作者：
Guzman, Gabriela, I;Sandberg, Troy E.;Feist, Adam M.
有证据表明，新的酶功能是从祖先酶的低水平混杂活动进化而来的。然而，这些副活动如何促进系统级适应的进化动力学和生理机制尚未得到很好的表征。此外，关于生物混杂反应集或地下代谢的知识是否有助于预测代谢适应的遗传基础，还有待检验。在这里，我们采用地下代谢计算模型和实验室进化实验来研究酶乱交在大肠杆菌K-12 MG1655在预测的非天然底物上获得和优化生长中的作用。在大约20代之后，进化的种群反复获得了在五种预测的非本地底物上生长的能力——d -葡萄糖、d -2-脱氧核糖、d -阿拉伯糖、m-酒石酸盐和琥珀酸单甲基。改变的滥交活动被证明直接参与了高效通路的建立。结构突变使酶底物的周转率向新的底物转移，同时保留了对原底物的偏好。最后，通过酶乱交代谢的基因组尺度模型模拟，准确预测了表型创新背后的基因。
Evidence suggests that novel enzyme functions evolved from low-level promiscuous activities in ancestral enzymes. Yet, the evolutionary dynamics and physiological mechanisms of how such side activities contribute to systems-level adaptations are not well characterized. Furthermore, it remains untested whether knowledge of an organism's promiscuous reaction set, or underground metabolism, can aid in forecasting the genetic basis of metabolic adaptations. Here, we employ a computational model of underground metabolism and laboratory evolution experiments to examine the role of enzyme promiscuity in the acquisition and optimization of growth on predicted non-native substrates in Escherichia coli K-12 MG1655. After as few as approximately 20 generations, evolved populations repeatedly acquired the capacity to grow on five predicted non-native substrates-D-lyxose, D-2-deoxyribose, D-arabinose, m-tartrate, and monomethyl succinate. Altered promiscuous activities were shown to be directly involved in establishing high-efficiency pathways. Structural mutations shifted enzyme substrate turnover rates toward the new substrate while retaining a preference for the primary substrate. Finally, genes underlying the phenotypic innovations were accurately predicted by genome-scale model simulations of metabolism with enzyme promiscuity.