感受态还是芽胞？细胞命运决定的遗传调控网络

Sporulation or competence development? A genetic regulatory network model of cell-fate determination in Bacillus subtilis

摘要:

枯草芽胞杆菌作为一般认为安全 (GRAS，Generally recognized as safe) 菌株，被广泛应用于饲料、食品、生物防治等领域，同时，枯草芽胞杆菌作为表达宿主在工业酶的应用中扮演重要角色。然而，低效的芽胞形成率与感受态效率极大限制了枯草芽胞杆菌的应用潜力。尽管已有大量关于芽胞形成与感受态形成的分子遗传机制的研究报道，但是通过遗传改造提高枯草芽胞杆菌芽胞形成率与感受态效率的研究报道并不多。可能的原因是芽胞形成与感受态形成作为枯草芽胞杆菌生长后期两个主要的发育事件，受胞内复杂的遗传调控机制操纵，且两个遗传通路之间存在相互调控关系，对遗传改造工作形成挑战。随着基因工程与代谢工程研究的不断发展，积累了大量关于细胞生长、代谢与发育等方面的遗传信息，通过综合这些遗传信息构建细胞遗传调控网络，用于指导生产实践，已经成为当前研究的热点之一。基于此，本文简要概述了枯草芽胞杆菌芽胞形成和感受态形成的遗传通路，初步探讨了芽胞形成与感受态形成之间的遗传调控网络，及细胞在生长后期的遗传决定机制，并讨论了该遗传调控网络对枯草芽孢杆菌及其近缘种应用研究的指导作用。

Abstract:

Bacillus subtilis is a generally recognized as safe (GRAS) strain that has been widely used in industries including fodder, food, and biological control. In addition, B. subtilis expression system also plays a significant role in the production of industrial enzymes. However, its application is limited by its low sporulation frequency and transformation efficiency. Immense studies have been done on interpreting the molecular mechanisms of sporulation and competence development, whereas only few of them were focused on improving sporulation frequency and transformation efficiency of B. subtilis by genetic modification. The main challenge is that sporulation and competence development, as the two major developmental events in the stationary phase of B. subtilis, are regulated by the complicated intracellular genetic regulatory systems. In addition, mutual regulatory mechanisms also exist in these two developmental events. With the development of genetic and metabolic engineering, constructing genetic regulatory networks is currently one of the most attractive research fields, together with the genetic information of cell growth, metabolism, and development, to guide the industrial application. In this review, the mechanisms of sporulation and competence development of B. subtilis, their interactions, and the genetic regulation of cell growth were interpreted. In addition, the roles of these regulatory networks in guiding basic and applied research of B. subtilis and its related species were discussed.