LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France
Appl Environ Microbiol. 2019 Jul 18;85(15). doi: 10.1128/AEM.00768-19. Print 2019 Aug 1.
In this work, we shed light on the metabolism of dihydroxyacetone (DHA), a versatile, ubiquitous, and important intermediate for various chemicals in industry, by analyzing its metabolism at the system level in Using constraint-based modeling, we show that the growth of on DHA is suboptimal and identify the potential causes. Nuclear magnetic resonance analysis shows that DHA is degraded nonenzymatically into substrates known to be unfavorable to high growth rates. Transcriptomic analysis reveals that DHA promotes genes involved in biofilm formation, which may reduce the bacterial growth rate. Functional analysis of the genes involved in DHA metabolism proves that under the aerobic conditions used in this study, DHA is mainly assimilated via the dihydroxyacetone kinase pathway. In addition, these results show that the alternative routes of DHA assimilation (i.e., the glycerol and fructose-6-phosphate aldolase pathways) are not fully activated under our conditions because of anaerobically mediated hierarchical control. These pathways are therefore certainly unable to sustain fluxes as high as the ones predicted for optimal aerobic growth on DHA. Overexpressing some of the genes in these pathways releases these constraints and restores the predicted optimal growth on DHA. DHA is an attractive triose molecule with a wide range of applications, notably in cosmetics and the food and pharmaceutical industries. DHA is found in many species, from microorganisms to humans, and can be used by as a growth substrate. However, knowledge about the mechanisms and regulation of this process is currently lacking, motivating our investigation of DHA metabolism in We show that under aerobic conditions, growth on DHA is far from optimal and is hindered by chemical, hierarchical, and possibly allosteric constraints. We show that optimal growth on DHA can be restored by releasing the hierarchical constraint. These results improve our understanding of DHA metabolism and are likely to help unlock biotechnological applications involving DHA as an intermediate, such as the bioconversion of glycerol or C substrates into value-added chemicals.
在这项工作中，我们通过在系统水平上分析其代谢作用，揭示了二羟丙酮（DHA）的代谢途径。DHA 是一种多功能、普遍存在且重要的工业化学中间体。利用基于约束的建模方法，我们表明在 DHA 上的生长是次优的，并确定了潜在的原因。核磁共振分析表明，DHA 非酶促降解为已知不利于高生长速率的底物。转录组分析揭示了 DHA 促进了生物膜形成相关基因的表达，这可能会降低细菌的生长速率。DHA 代谢相关基因的功能分析证明，在本研究中使用的需氧条件下，DHA 主要通过二羟丙酮激酶途径被同化。此外，这些结果表明，DHA 同化的替代途径（即甘油和果糖-6-磷酸醛缩酶途径）在我们的条件下没有被完全激活，因为这是由厌氧介导的层次控制引起的。因此，这些途径肯定无法维持预测的在有氧条件下以 DHA 为最佳生长底物的高通量。过表达这些途径中的一些基因可以释放这些限制并恢复预测的最佳 DHA 生长。DHA 是一种具有广泛应用的有吸引力的三碳分子，特别是在化妆品、食品和制药行业。DHA 存在于许多物种中，从微生物到人，并且可以被 用作生长底物。然而，目前对这一过程的机制和调控知之甚少，这促使我们研究 中的 DHA 代谢。我们表明，在需氧条件下， 以 DHA 为生长底物的生长远非最佳，并且受到化学、层次和可能的变构限制的阻碍。我们表明，通过释放层次限制可以恢复 DHA 的最佳生长。这些结果提高了我们对 DHA 代谢的理解，并且可能有助于释放涉及 DHA 作为中间体的生物技术应用，例如将甘油或 C 底物生物转化为高附加值化学品。
