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基于约束的建模方法捕捉到了普通脱硫弧菌的代谢多功能性。

Constraint-based modelling captures the metabolic versatility of Desulfovibrio vulgaris.

机构信息

Department of Civil and Environmental Engineering, University of Washington, Seattle, WA, USA.

Institute for Systems Biology, Seattle, WA, USA.

出版信息

Environ Microbiol Rep. 2018 Apr;10(2):190-201. doi: 10.1111/1758-2229.12619. Epub 2018 Feb 19.

DOI:10.1111/1758-2229.12619
PMID:29377633
Abstract

A refined Desulfovibrio vulgaris Hildenborough flux balance analysis (FBA) model (iJF744) was developed, incorporating 1016 reactions that include 744 genes and 951 metabolites. A draft model was first developed through automatic model reconstruction using the ModelSeed Server and then curated based on existing literature. The curated model was further refined by incorporating three recently proposed redox reactions involving the Hdr-Flx and Qmo complexes and a lactate dehydrogenase (LdhAB, DVU 3027-3028) indicated by mutation and transcript analyses to serve electron transfer reactions central to syntrophic and respiratory growth. Eight different variations of this model were evaluated by comparing model predictions to experimental data determined for four different growth conditions - three for sulfate respiration (with lactate, pyruvate or H /CO -acetate) and one for fermentation in syntrophic coculture. The final general model supports (i) a role for Hdr-Flx in the oxidation of DsrC and ferredoxin, and reduction of NAD in a flavin-based electron confurcating reaction sequence, (ii) a function of the Qmo complex in receiving electrons from the menaquinone pool and potentially from ferredoxin to reduce APS and (iii) a reduction of the soluble DsrC by LdhAB and a function of DsrC in electron transfer reactions other than sulfite reduction.

摘要

我们构建了一个精细化的脱硫弧菌 Hildenborough 通量平衡分析(FBA)模型(iJF744),其中包含了 1016 个反应,涉及 744 个基因和 951 种代谢物。该模型最初是通过 ModelSeed Server 进行自动模型重建得到的,然后根据现有文献进行了校正。通过整合最近提出的涉及 Hdr-Flx 和 Qmo 复合物的三个氧化还原反应,以及突变和转录分析表明参与电子传递反应的乳酸脱氢酶(LdhAB,DVU 3027-3028),对校正后的模型进行了进一步的精细化处理,这些反应对共生和呼吸生长至关重要。我们通过将模型预测与四种不同生长条件下的实验数据进行比较,评估了该模型的八种不同变体,其中三种用于硫酸盐呼吸(分别使用乳酸盐、丙酮酸或 H/CO-乙酸盐),一种用于在共生共培养物中进行发酵。最终的通用模型支持:(i)Hdr-Flx 在 DsrC 和黄素辅因子的氧化以及基于黄素的电子分叉反应序列中 NAD 的还原中发挥作用;(ii)Qmo 复合物在从menaquinone 池和潜在的来自铁氧还蛋白中接收电子,以还原 APS 中的作用;(iii)LdhAB 将可溶性 DsrC 还原,并证明 DsrC 在除亚硫酸盐还原以外的电子传递反应中的功能。

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