Alignment of microbial fitness with engineered product formation: obligatory coupling between acetate production and photoautotrophic growth.
Alignment of microbial fitness with engineered product formation: obligatory coupling between acetate production and photoautotrophic growth.
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DOI：
10.1186/s13068-018-1037-8
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发表时间：
2018
影响因子：
6.3
通讯作者：
Branco Dos Santos F
中科院分区：
文献类型：
--
作者：
Du W;Jongbloets JA;van Boxtel C;Pineda Hernández H;Lips D;Oliver BG;Hellingwerf KJ;Branco Dos Santos F
微生物生物工程通过提供可持续的、新颖的、具有成本效益的生产管道，有可能成为人类社会未来发展的关键贡献者。然而，基因工程菌株的持续生产力往往是一个挑战，因为自发的非生产突变体往往生长得更快，并接管了种群。迫切需要新的策略来防止这一问题的应变不稳定。在这项研究中，我们提出了一种适用于所有微生物生产系统的新策略，其中基因组尺度的代谢模型是可用的，该模型将天然代谢物的生产与生物量的形成相一致。基于成熟的基于约束的分析技术，如OptKnock和FVA，我们开发了一个硅管道- fruits，专门用于“发现可用于开发副产物的反应”。它分析了一个代谢网络，以识别合成代谢中产生的化合物，这些化合物适合通过删除它们的再利用途径与生长相结合，并计算它们各自的生物量和产物形成率。当应用于可持续生物生产模式蓝藻Synechocystis sp. PCC6803时，共鉴定出9个目标代谢物。我们对其中一种化合物醋酸酯进行了测试，醋酸酯广泛用于工业应用。模型引导的工程菌株显示出醋酸生产和光自养生长之间的强制性耦合。此外，通过进行长时间的除浊器培养，证实了该菌株醋酸盐产量的稳定性。这项工作证明了一种新的方法来稳定生产目标化合物的蓝藻，最终在一个光自养生长偶联细胞工厂的第一份报告。所开发的方法是通用的，可以很容易地扩展到任何其他模拟微生物生产系统。本文的在线版本（10.1186/s13068-018-1037-8）包含补充内容，仅供授权用户使用。
Microbial bioengineering has the potential to become a key contributor to the future development of human society by providing sustainable, novel, and cost-effective production pipelines. However, the sustained productivity of genetically engineered strains is often a challenge, as spontaneous non-producing mutants tend to grow faster and take over the population. Novel strategies to prevent this issue of strain instability are urgently needed. In this study, we propose a novel strategy applicable to all microbial production systems for which a genome-scale metabolic model is available that aligns the production of native metabolites to the formation of biomass. Based on well-established constraint-based analysis techniques such as OptKnock and FVA, we developed an in silico pipeline—FRUITS—that specifically ‘Finds Reactions Usable in Tapping Side-products’. It analyses a metabolic network to identify compounds produced in anabolism that are suitable to be coupled to growth by deletion of their re-utilization pathway(s), and computes their respective biomass and product formation rates. When applied to Synechocystis sp. PCC6803, a model cyanobacterium explored for sustainable bioproduction, a total of nine target metabolites were identified. We tested our approach for one of these compounds, acetate, which is used in a wide range of industrial applications. The model-guided engineered strain shows an obligatory coupling between acetate production and photoautotrophic growth as predicted. Furthermore, the stability of acetate productivity in this strain was confirmed by performing prolonged turbidostat cultivations. This work demonstrates a novel approach to stabilize the production of target compounds in cyanobacteria that culminated in the first report of a photoautotrophic growth-coupled cell factory. The method developed is generic and can easily be extended to any other modeled microbial production system. The online version of this article (10.1186/s13068-018-1037-8) contains supplementary material, which is available to authorized users.
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影响因子：
2.9
作者：
Cheah, Yi Ern;Albers, Stevan C.;Peebles, Christie A. M.
通讯作者：
Peebles, Christie A. M.
影响因子：
11.3
作者：
Bachmann, Herwig;Molenaar, Douwe;Teusink, Bas
通讯作者：
Teusink, Bas
影响因子：
--
作者：
Kim J;Reed JL
通讯作者：
Reed JL
DOI：
10.1073/pnas.1221194110
发表时间：
2013-03-05
影响因子：
11.1
作者：
Allahverdiyeva, Yagut;Mustila, Henna;Aro, Eva-Mari
通讯作者：
Aro, Eva-Mari
影响因子：
6.4
作者：
Erdrich P;Knoop H;Steuer R;Klamt S
通讯作者：
Klamt S