Genetic redundancy of 4-hydroxybenzoate 3-hydroxylase genes ensures the catabolic safety of Pigmentiphaga sp. H8 in 3-bromo-4-hydroxybenzoate-contaminated habitats
Genetic redundancy of 4-hydroxybenzoate 3-hydroxylase genes ensures the catabolic safety of Pigmentiphaga sp. H8 in 3-bromo-4-hydroxybenzoate-contaminated habitats
复制标题
4-羟基苯甲酸3-羟化酶基因的遗传冗余确保了 Pigmentiphaga sp 的分解代谢安全。
DOI：
10.1111/1462-2920.16141
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发表时间：
2022-08-04
影响因子：
5.1
通讯作者：
Jiang, Jiandong
中科院分区：
文献类型：
--
作者：
Chen, Kai;Xu, Xihui;Jiang, Jiandong
遗传冗余普遍存在于生物体中，在生物多样性的进化和对环境扰动的适应中发挥着重要作用。然而，遗传冗余在克服结构类似物引起的代谢紊乱方面的选择性优势几乎没有受到关注。在Pigentiphaga sp.中发现了3个4-羟基苯甲酸3-羟基酶(PHBH)基因(phbh1类似于3)的功能差异。菌株H8。Phbh1/phbh2基因负责3-溴-4-羟基苯甲酸(3-溴-4-HB，人为污染物)的分解代谢，而phbh3主要负责4-羟基苯甲酸(4-HB，木质素的天然中间体)的分解代谢。3-溴-4-Hb通过竞争结合PHBH3抑制4-Hb的分解代谢，对H8细胞有毒性作用，尤其是在高浓度时。Phbh1/phbh2的存在不仅使菌株H8能够利用3-Br-4-Hb，而且保证了4-Hb的分解代谢安全。分子对接和定点突变分析表明，PHBH1/PHBH2的Val199和Phe384是3-Br4-Hb羟基化活性所必需的。系统发育分析表明，phbh1和phbh2起源于一个共同的祖先，并在菌株H8中特异进化以适应3-溴-4-Hb污染的生境，而phbh3独立进化。这项研究加深了我们对遗传冗余在原核生物代谢稳健性中的选择优势的理解，并揭示了驱动冗余基因在适应环境扰动时的差异进化的因素。
Genetic redundancy is prevalent in organisms and plays important roles in the evolution of biodiversity and adaptation to environmental perturbation. However, selective advantages of genetic redundancy in overcoming metabolic disturbance due to structural analogues have received little attention. Here, functional divergence of the three 4-hydroxybenzoate 3-hydroxylase (PHBH) genes (phbh1 similar to 3) was found in Pigmentiphaga sp. strain H8. The genes phbh1/phbh2 were responsible for 3-bromo-4-hydroxybenzoate (3-Br-4-HB, an anthropogenic pollutant) catabolism, whereas phbh3 was primarily responsible for 4-hydroxybenzoate (4-HB, a natural intermediate of lignin) catabolism. 3-Br-4-HB inhibited 4-HB catabolism by competitively binding PHBH3 and was toxic to strain H8 cells especially at high concentrations. The existence of phbh1/phbh2 not only enabled strain H8 to utilize 3-Br-4-HB but also ensured the catabolic safety of 4-HB. Molecular docking and site-directed mutagenesis analyses revealed that Val199 and Phe384 of PHBH1/PHBH2 were required for the hydroxylation activity towards 3-Br-4-HB. Phylogenetic analysis indicated that phbh1 and phbh2 originated from a common ancestor and evolved specifically in strain H8 to adapt to 3-Br-4-HB-contaminated habitats, whereas phbh3 evolved independently. This study deepens our understanding of selective advantages of genetic redundancy in prokaryote's metabolic robustness and reveals the factors driving the divergent evolution of redundant genes in adaptation to environmental perturbation.