Cofactor engineering in cyanobacteria to overcome imbalance between NADPH and NADH: A mini review

Park, Jong; Choi, Yun‐Nam

doi:10.1007/s11705-016-1591-1

Cited by 28 publications

(18 citation statements)

References 44 publications

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“…ATP is consumed by two separate processes: growth- and maintenance-associated reactions reach a threshold once growth is limited by the nitrogen abundance, while the recycling of precursors for the Calvin cycle follows the shape of light absorption throughout the day. In agreement with previous work ( Park and Choi, 2017 ), our model predicted higher rates of NADPH production than NADH.…”

Section: Resultssupporting

confidence: 92%

Dynamic Allocation of Carbon Storage and Nutrient-Dependent Exudation in a Revised Genome-Scale Model of Prochlorococcus

et al. 2021

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Microbial life in the oceans impacts the entire marine ecosystem, global biogeochemistry and climate. The marine cyanobacterium Prochlorococcus, an abundant component of this ecosystem, releases a significant fraction of the carbon fixed through photosynthesis, but the amount, timing and molecular composition of released carbon are still poorly understood. These depend on several factors, including nutrient availability, light intensity and glycogen storage. Here we combine multiple computational approaches to provide insight into carbon storage and exudation in Prochlorococcus. First, with the aid of a new algorithm for recursive filling of metabolic gaps (ReFill), and through substantial manual curation, we extended an existing genome-scale metabolic model of Prochlorococcus MED4. In this revised model (iSO595), we decoupled glycogen biosynthesis/degradation from growth, thus enabling dynamic allocation of carbon storage. In contrast to standard implementations of flux balance modeling, we made use of forced influx of carbon and light into the cell, to recapitulate overflow metabolism due to the decoupling of photosynthesis and carbon fixation from growth during nutrient limitation. By using random sampling in the ensuing flux space, we found that storage of glycogen or exudation of organic acids are favored when the growth is nitrogen limited, while exudation of amino acids becomes more likely when phosphate is the limiting resource. We next used COMETS to simulate day-night cycles and found that the model displays dynamic glycogen allocation and exudation of organic acids. The switch from photosynthesis and glycogen storage to glycogen depletion is associated with a redistribution of fluxes from the Entner–Doudoroff to the Pentose Phosphate pathway. Finally, we show that specific gene knockouts in iSO595 exhibit dynamic anomalies compatible with experimental observations, further demonstrating the value of this model as a tool to probe the metabolic dynamic of Prochlorococcus.

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Section: Resultssupporting

confidence: 92%

Dynamic Allocation of Carbon Storage and Nutrient-Dependent Exudation in a Revised Genome-Scale Model of Prochlorococcus

et al. 2021

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“…The presented examples indicate a limited applicability of phototrophs for NADH-dependent reactions, which only indirectly couple to the photosynthetic light reaction. Application of such enzymes in cyanobacteria/green algae requires either a change in enzymatic cofactor preference ( Park and Choi, 2017 ; Wang et al, 2017 ) or redirection of electrons towards NADH. Implementation of NADH-dependent nitrate assimilation led to enhanced NADH production, supporting the target pathways and finally the NADPH-dependent butanol formation ( Purdy et al, 2022 ).…”

Section: Pathway Engineeringmentioning

confidence: 99%

Exploitation of Hetero- and Phototrophic Metabolic Modules for Redox-Intensive Whole-Cell Biocatalysis

Theodosiou

Tüllinghoff

Toepel

et al. 2022

Front. Bioeng. Biotechnol.

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The successful realization of a sustainable manufacturing bioprocess and the maximization of its production potential and capacity are the main concerns of a bioprocess engineer. A main step towards this endeavor is the development of an efficient biocatalyst. Isolated enzyme(s), microbial cells, or (immobilized) formulations thereof can serve as biocatalysts. Living cells feature, beside active enzymes, metabolic modules that can be exploited to support energy-dependent and multi-step enzyme-catalyzed reactions. Metabolism can sustainably supply necessary cofactors or cosubstrates at the expense of readily available and cheap resources, rendering external addition of costly cosubstrates unnecessary. However, for the development of an efficient whole-cell biocatalyst, in depth comprehension of metabolic modules and their interconnection with cell growth, maintenance, and product formation is indispensable. In order to maximize the flux through biosynthetic reactions and pathways to an industrially relevant product and respective key performance indices (i.e., titer, yield, and productivity), existing metabolic modules can be redesigned and/or novel artificial ones established. This review focuses on whole-cell bioconversions that are coupled to heterotrophic or phototrophic metabolism and discusses metabolic engineering efforts aiming at 1) increasing regeneration and supply of redox equivalents, such as NAD(P/H), 2) blocking competing fluxes, and 3) increasing the availability of metabolites serving as (co)substrates of desired biosynthetic routes.

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“…As the molecules of NADPH generated from photosynthesis are much more than the NADH generated from catabolism, NADPH is the dominant form of reducing equivalent in cyanobacteria, and the NADH pool in cyanobacteria is lower than its NADPH pool under photoautotrophic conditions [ 8 – 11 ]. Consequently, NADH-dependent enzymes are less active than NADPH-dependent ones in cyanobacteria due to a shortage of NADH [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Dehydrogenases are involved in the biosynthesis of many chemicals [ 14 , 15 ]. Most dehydrogenases in nature prefer to utilize NADH as a cofactor, indicating these NADH-dependent dehydrogenases might not work efficiently in cyanobacteria [ 12 – 14 ]. Several approaches have been developed to tackle this problem [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Most dehydrogenases in nature prefer to utilize NADH as a cofactor, indicating these NADH-dependent dehydrogenases might not work efficiently in cyanobacteria [ 12 – 14 ]. Several approaches have been developed to tackle this problem [ 14 ]. This includes finding and applying NADPH-dependent dehydrogenases [ 12 , 13 ], using NADH-dependent dehydrogenases co-expressed with soluble transhydrogenase to convert NADPH into NADH [ 16 , 17 ], or changing the cofactor preference of the dehydrogenases from NADPH to NADH through site-directed mutagenesis [ 15 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Over-expression of an electron transport protein OmcS provides sufficient NADH for d-lactate production in cyanobacterium

Meng

Zhang

Zhu

et al. 2021

Biotechnol Biofuels

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Background An efficient supply of reducing equivalent is essential for chemicals production by engineered microbes. In phototrophic microbes, the NADPH generated from photosynthesis is the dominant form of reducing equivalent. However, most dehydrogenases prefer to utilize NADH as a cofactor. Thus, sufficient NADH supply is crucial to produce dehydrogenase-derived chemicals in cyanobacteria. Photosynthetic electron is the sole energy source and excess electrons are wasted in the light reactions of photosynthesis. Results Here we propose a novel strategy to direct the electrons to generate more ATP from light reactions to provide sufficient NADH for lactate production. To this end, we introduced an electron transport protein-encoding gene omcS into cyanobacterium Synechococcus elongatus UTEX 2973 and demonstrated that the introduced OmcS directs excess electrons from plastoquinone (PQ) to photosystem I (PSI) to stimulate cyclic electron transfer (CET). As a result, an approximately 30% increased intracellular ATP, 60% increased intracellular NADH concentrations and up to 60% increased biomass production with fourfold increased d-lactate production were achieved. Comparative transcriptome analysis showed upregulation of proteins involved in linear electron transfer (LET), CET, and downregulation of proteins involved in respiratory electron transfer (RET), giving hints to understand the increased levels of ATP and NADH. Conclusions This strategy provides a novel orthologous way to improve photosynthesis via enhancing CET and supply sufficient NADH for the photosynthetic production of chemicals.

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Cofactor engineering in cyanobacteria to overcome imbalance between NADPH and NADH: A mini review

Cited by 28 publications

References 44 publications

Dynamic Allocation of Carbon Storage and Nutrient-Dependent Exudation in a Revised Genome-Scale Model of Prochlorococcus

Dynamic Allocation of Carbon Storage and Nutrient-Dependent Exudation in a Revised Genome-Scale Model of Prochlorococcus

Exploitation of Hetero- and Phototrophic Metabolic Modules for Redox-Intensive Whole-Cell Biocatalysis

Over-expression of an electron transport protein OmcS provides sufficient NADH for d-lactate production in cyanobacterium

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