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Efficient production of 2′-fucosyllactose from fructose through metabolically engineered recombinant Escherichia coli
2024
Background
The biosynthesis of human milk oligosaccharides (HMOs) using several microbial systems has garnered considerable interest for their value in pharmaceutics and food industries. 2′-Fucosyllactose (2′-FL), the most abundant oligosaccharide in HMOs, is usually produced using chemical synthesis with a complex and toxic process. Recombinant
E. coli
strains have been constructed by metabolic engineering strategies to produce 2′-FL, but the low stoichiometric yields (2′-FL/glucose or glycerol) are still far from meeting the requirements of industrial production. The sufficient carbon flux for 2′-FL biosynthesis is a major challenge. As such, it is of great significance for the construction of recombinant strains with a high stoichiometric yield.
Results
In the present study, we designed a 2′-FL biosynthesis pathway from fructose with a theoretical stoichiometric yield of 0.5 mol 2′-FL/mol fructose. The biosynthesis of 2′-FL involves five key enzymes: phosphomannomutase (ManB), mannose-1-phosphate guanylytransferase (ManC), GDP-
d
-mannose 4,6-dehydratase (Gmd), and GDP-
l
-fucose synthase (WcaG), and α-1,2-fucosyltransferase (FucT). Based on starting strain SG104, we constructed a series of metabolically engineered
E. coli
strains by deleting the key genes
pfkA
,
pfkB
and
pgi
, and replacing the original promoter of
lacY
. The co-expression systems for ManB, ManC, Gmd, WcaG, and FucT were optimized, and nine FucT enzymes were screened to improve the stoichiometric yields of 2′-FL. Furthermore, the gene
gapA
was regulated to further enhance 2′-FL production, and the highest stoichiometric yield (0.498 mol 2′-FL/mol fructose) was achieved by using recombinant strain RFL38 (SG104
ΔpfkAΔpfkBΔpgi119-lacYΔwcaF
::
119-gmd-wcaG-manC-manB
,
119
-AGGAGGAGG-
gapA
, harboring plasmid P30). In the scaled-up reaction, 41.6 g/L (85.2 mM) 2′-FL was produced by a fed-batch bioconversion, corresponding to a stoichiometric yield of 0.482 mol 2′-FL/mol fructose and 0.986 mol 2′-FL/mol lactose.
Conclusions
The biosynthesis of 2′-FL using recombinant
E. coli
from fructose was optimized by metabolic engineering strategies. This is the first time to realize the biological production of 2′-FL production from fructose with high stoichiometric yields. This study also provides an important reference to obtain a suitable distribution of carbon flux between 2′-FL synthesis and glycolysis.
Journal Article
Trilemma association of energy consumption, carbon emission, and economic growth of BRICS and OECD regions: quantile regression estimation
by
Nawaz, Muhammad Atif
,
Ehsanullah, Syed
,
Shair, Faluk
in
Aquatic Pollution
,
Atmospheric Protection/Air Quality Control/Air Pollution
,
Autoregressive models
2021
Recent research has shown a huge impact of non-renewable energy (NRE) production on environmental health. In this context, this work analyzes the effects of GDP growth and long- and short-term consumption of renewable and non-renewable energy (RE and NRE, respectively) on carbon emission in BRICS and OECD economies. The quantile autoregressive distributed lag (QARDL) model was employed on the panel data from 1980 to 2016. Findings suggest a negative GDP-carbon emission correlation and a positive NRE-carbon emission correlation in the considered economies. Furthermore, carbon emission decreases with increase in gross capital formation, whereas trade openness does not have any significant effect on carbon emission. It has been determined that the application of the error correction method (ECM) has less effect on energy consumption as compared to the past levels and changes in energy consumption. In the long-term, a positive correlation of carbon emission and energy consumption is observed, whereas limited short-term effects of energy consumption on carbon emission are observed. Therefore, an RE-based energy production approach is recommended in the selected region for the future projects.
Journal Article
Odoribacter splanchnicus rescues aging-related intestinal P-glycoprotein damage via GDP-L-fucose secretion
Intestinal P-glycoprotein (P-gp/
ABCB1
) is a key barrier limiting xenobiotic absorption, yet its functional decline with aging is poorly understood. Here, we show that gut microbiota dysbiosis contributes to age-associated P-gp deficiency. Integrated multi-omics analyses of human cohorts and murine models identify
Odoribacter splanchnicus
(
O. splanchnicus
) as a key commensal species whose depletion impairs intestinal P-gp function. Mechanistically,
O. splanchnicus
encodes GDP-mannose 4, 6-dehydratase (GMDS) and GDP-L-fucose synthase (TSTA3), enabling microbial biosynthesis of GDP-L-fucose. This metabolite directly promotes phosphorylation of the eukaryotic translation initiation factor 4E (eIF4E) and activates c-Jun-driven
ABCB1
expression, thereby restoring xenobiotic efflux. These findings establish a microbiota-metabolite-transporter signaling axis that maintains intestinal detoxification, suggesting that targeting either microbes or metabolites could help prevent adverse drug reactions in older adults.
Here, with multi-omics analyses of human cohorts and murine models, the authors identify
Odoribacter splanchnicus
depletion to impair intestinal P-glycoprotein function via loss of microbial, GDP-L-fucose, which in turn promotes eIF4E phosphorylation and c-Jun–driven ABCB1 expression, maintaining xenobiotic efflux.
Journal Article
Global 1 km × 1 km gridded revised real gross domestic product and electricity consumption during 1992–2019 based on calibrated nighttime light data
by
Song, Malin
,
Gao, Ming
,
Liu, Yu
in
Electricity
,
Gross Domestic Product
,
Meteorological satellites
2022
As fundamental data, gross domestic product (GDP) and electricity consumption can be used to effectively evaluate economic status and living standards of residents. Some scholars have estimated gridded GDP and electricity consumption. However, such gridded data have shortcomings, including overestimating real GDP growth, ignoring the heterogeneity of the spatiotemporal dynamics of the grid, and limited time-span. Simultaneously, the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS) and National Polar-orbiting Partnership’s Visible Infrared Imaging Radiometer (NPP/VIIRS) nighttime light data, adopted in these studies as a proxy tool, still facing shortcomings, such as imperfect matching results, discontinuity in temporal and spatial changes. In this study, we employed a series of methods, such as a particle swarm optimization-back propagation (PSO-BP) algorithm, to unify the scales of DMSP/OLS and NPP/VIIRS images and obtain continuous 1 km × 1 km gridded nighttime light data during 1992–2019. Subsequently, from a revised real growth perspective, we employed a top-down method to calculate global 1 km × 1 km gridded revised real GDP and electricity consumption during 1992–2019 based on our calibrated nighttime light data.Measurement(s)GDP • electricty consumptionTechnology Type(s)machine learning
Journal Article
Evaluating the impact of GDP per capita on environmental degradation for G-20 economies: Does N-shaped environmental Kuznets curve exist?
by
Azam, Muhammad
,
Awan, Abdul Majid
in
Carbon dioxide
,
Carbon dioxide emissions
,
Development policy
2022
The extant literature reveals that scholars and policy makers are highly concerned about exploring the validity of the environmental Kuznets curve (EKC) hypothesis using a different set of variables with the prime objective of exploring environmental degradation issues related to sustainable economic development for different countries. We examine the validity of the EKC hypothesis for the five most influenced economies of the G-20 from 1993 to 2017 using GDP per capita and CO
2
emissions, along with some other variables, namely technological development, financial development (FD), energy use, and social globalization to avoid any misspecification in the empirical model. The LM bootstrap approach confirms the co-integration in the series, and the panel Driscoll–Kraay standard error method confirms that veto-power economies have an N-shaped relationship between CO
2
emissions and GDP per capita. Furthermore, empirical findings exhibit that technological advancement and energy consumption positively correlate with CO
2
emissions, whereas FD and social globalization attenuate environmental degradation. These empirical findings suggest that appropriate policies need to be designed for these sample countries, depending on their GDP per capita and CO
2
emissions levels. An environmentally friendly policy may be adopted to achieve sustainable development goals. Policymakers also need to implement a policy that encourages financial development and boosts technologies with fewer polluting characteristics.
Journal Article
The 2023 report of the Lancet Countdown on health and climate change: the imperative for a health-centred response in a world facing irreversible harms
by
Liu, Zhao
,
Obradovich, Nick
,
Napoli, Claudia di
in
Adaptation
,
Anthropogenic factors
,
Clean technology
2023
In 2022, the Lancet Countdown warned that people's health is at the mercy of fossil fuels and stressed the transformative opportunity of jointly tackling the concurrent climate change, energy, cost-of-living, and health crises for human health and wellbeing. Harnessing the rapidly advancing science of detection and attribution, new analysis shows that over 60% of the days that reached health-threatening high temperatures in 2020 were made more than twice as likely to occur due to anthropogenic climate change (indicator 1.1.5); and heat-related deaths of people older than 65 years increased by 85% compared with 1990–2000, substantially higher than the 38% increase that would have been expected had temperatures not changed (indicator 1.1.5). [...]those countries that have historically contributed the least to climate change are bearing the brunt of its health impacts—both a reflection and a direct consequence of the structural inequities that lie within the root causes of climate change. The 2022 Lancet Countdown report highlighted the opportunity to accelerate the transition away from health-harming fossil fuels in response to the global energy crisis.
Journal Article
An Evolutionary Game Theory Study for Construction and Demolition Waste Recycling Considering Green Development Performance under the Chinese Government’s Reward–Penalty Mechanism
2020
The low efficiency of the closed-loop supply chain in construction and demolition waste (CDW) recycling has restricted the green development of China’s construction industry. Additionally, the government’s reward–penalty mechanism has a huge influence on green development. This study aimed to investigate the effect of green development performance (GDP) and the government’s reward–penalty mechanism on the decision-making process of production and recycling units, as well as to reveal the optimal strategies under different conditions. Therefore, the strategies’ evolutionary paths of production and recycling units were investigated by using evolutionary game theory. Firstly, an evolutionary game model between production units and recycling units was proposed under the government’s reward–penalty mechanism. Then, the evolutionary stability strategies in different scenarios were discussed. Finally, the effects of the relevant parameters on the evolutionary paths of the game model were analyzed using numerical simulations. The main conclusions are as follows. (1) When the range of GDP changes, the evolutionary stable strategy changes accordingly. GDP plays a positive role in promoting the high-quality development of the CDW recycling supply chain, but an increase in GDP can easily lead to the simultaneous motivation of free-riding. (2) The government’s reward–penalty mechanism effectively regulates the decision-making process of production and recycling units. An increase in the subsidy rate and supervision probability helps to reduce free-riding behavior. Moreover, the incentive effect of the subsidy probability on recycling units is more obvious, while the effect of the supervision probability on improving the motivation of active participation for production units is more remarkable. This paper not only provides a decision-making basis to ensure production and recycling units to make optimal strategy choices under different conditions but also provides a reference for the government to formulate a reasonable reward–penalty mechanism that is conducive to a macro-control market.
Journal Article
Convergence in the Spanish and Portuguese NUTS 3 regions: an analysis of the period 2000-2019
by
Flores Polán, María Gema
,
Fuentes Calle, Gemma
,
DE LA MACORRA Y CANO, LUÍS FERNANDO
in
Economic convergence
,
Portugal
,
Spain
2025
The objective of this paper is to examine the convergence of economic activity between the various NUTS 3 regions of the Iberian Peninsula over the period 2000-2019. An analysis of the GDP (PPS) per capita of Spanish and Portuguese provinces was conducted with the help of different usual statistical and econometric methods of σ, β and γ. This was done to confirm the existence or non-existence of economic convergence in the period under analysis. The results revealed the existence of economic convergence between the Portuguese and Spanish provinces. In addition, they showed that more than half of the territory analysed was characterised by a scenario of poverty. El objetivo del presente trabajo es explorar la convergencia de la actividad económica entre las distintas regiones NUTS 3 de la Península Ibérica durante el periodo 2000-2019, a partir de un análisis del PIB (PPS) per cápita de provincias españolas y portuguesas, con ayuda de los diferentes métodos estadísticos y econométricos habituales de σ, β y γ. Para así poder confirmar la existencia o no de convergencia económica en el periodo analizado. Los resultados nos revelan la existencia de convergencia económica entre las provincias portuguesas y españolas. Además de mostrarnos un escenario de pobreza en más de la mitad del territorio analizado.
Journal Article
Investigating the environmental Kuznets curve hypothesis: the role of tourism and ecological footprint
by
Ozturk, Ilhan
,
Al-Mulali, Usama
,
Saboori, Behnaz
in
Aquatic Pollution
,
Atmospheric Protection/Air Quality Control/Air Pollution
,
Climate change
2016
The main objective of this study is to examine the environmental Kuznets curve (EKC) hypothesis by utilizing the ecological footprint as an environment indicator and GDP from tourism as the economic indicator. To achieve this goal, an environmental degradation model is established during the period of 1988–2008 for 144 countries. The results from the time series generalized method of moments (GMM) and the system panel GMM revealed that the number of countries that have a negative relationship between the ecological footprint and its determinants (GDP growth from tourism, energy consumption, trade openness, and urbanization) is more existent in the upper middle- and high-income countries. Moreover, the EKC hypothesis is more present in the upper middle- and high-income countries than the other income countries. From the outcome of this research, a number of policy recommendations were provided for the investigated countries.
Journal Article