scholarly journals Computational protein design enables a novel one-carbon assimilation pathway

2015 ◽  
Vol 112 (12) ◽  
pp. 3704-3709 ◽  
Author(s):  
Justin B. Siegel ◽  
Amanda Lee Smith ◽  
Sean Poust ◽  
Adam J. Wargacki ◽  
Arren Bar-Even ◽  
...  
Keyword(s):  
Protein Design ◽  
Biosynthetic Pathway ◽  
Carbon Fixation ◽  
Carbon Assimilation ◽  
Dihydroxyacetone Phosphate ◽  
Design Tools ◽  
Chemical Transformations ◽  
Central Metabolism ◽  
Naturally Occurring

We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of FLS enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, FLS converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.

scholarly journals The global mass and average rate of rubisco

2019 ◽  
Vol 116 (10) ◽  
pp. 4738-4743 ◽  
Author(s):  
Yinon M. Bar-On ◽  
Ron Milo
Keyword(s):  
Total Mass ◽  
Carbon Fixation ◽  
Average Rate ◽  
Carbon Assimilation ◽  
Dry Weight ◽  
Effective Rate ◽  
Terrestrial Plants ◽  
Bisphosphate Carboxylase ◽  
Catalytic Rate

Photosynthetic carbon assimilation enables energy storage in the living world and produces most of the biomass in the biosphere. Rubisco (d-ribulose 1,5-bisphosphate carboxylase/oxygenase) is responsible for the vast majority of global carbon fixation and has been claimed to be the most abundant protein on Earth. Here we provide an updated and rigorous estimate for the total mass of Rubisco on Earth, concluding it is ≈0.7 Gt, more than an order of magnitude higher than previously thought. We find that >90% of Rubisco enzymes are found in the ≈2 × 1014m2of leaves of terrestrial plants, and that Rubisco accounts for ≈3% of the total mass of leaves, which we estimate at ≈30 Gt dry weight. We use our estimate for the total mass of Rubisco to derive the effective time-averaged catalytic rate of Rubisco of ≈0.03 s−1on land and ≈0.6 s−1in the ocean. Compared with the maximal catalytic rate observed in vitro at 25 °C, the effective rate in the wild is ≈100-fold slower on land and sevenfold slower in the ocean. The lower ambient temperature, and Rubisco not working at night, can explain most of the difference from laboratory conditions in the ocean but not on land, where quantification of many more factors on a global scale is needed. Our analysis helps sharpen the dramatic difference between laboratory and wild environments and between the terrestrial and marine environments.

scholarly journals Tandem mass spectrum similarity-based network analysis using 13C-labeled and non-labeled metabolome data to identify the biosynthesis pathway of the blood pressure-lowering asparagus metabolite asparaptine A

2021 ◽  
Author(s):  
Ryo Nakabayashi ◽  
Yutaka Yamada ◽  
Tomoko Nishizawa ◽  
Tetsuya Mori ◽  
Takashi Asano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Network Analysis ◽  
Biosynthetic Pathway ◽  
Oral Feeding ◽  
Asparagus Officinalis ◽  
Tandem Mass ◽  
Naturally Occurring ◽  
Pressure Lowering ◽  
Mouse Species

AbstractAsparaptine, a conjugate of arginine and asparagusic acid, was found in asparagus (Asparagus officinalis) as a naturally occurring inhibitor of angiotensin-converting enzyme (ACE) in vitro. The biosynthetic pathway to asparaptine is largely unknown; however, it is suggested that asparagusic acid may be biosynthesized from valine. To determine which metabolites are involved in the asparaptine biosynthetic pathway, we performed tandem mass spectrometry similarity-based metabolome network analysis using 13C labeled and non-labeled valine-fed asparagus calluses. We determined that valine is used as a starting material, S(2-carboxy-n-propyl)-cysteine as an intermediate, and two new metabolites as asparaptine analogs, lysine- and histidine-type conjugates, are involved in the pathway. Asparaptine was therefore renamed asparaptine A (arginine type), and the two analogs were named asparaptines B (lysine type) and C (histidine type). Oral feeding of asparaptine A to a hypertensive mouse species showed that this metabolite lowers both blood pressure and heart rate within two hours and both of which were back to normal two days later. These results suggest that asparaptine A may not only have effects as an ACE inhibitor, but also has β-antagonistic effects, which are well-known to be preventive for cardiovascular diseases.

scholarly journals Efficient Regulation of CO2 Assimilation Enables Greater Resilience to High Temperature and Drought in Maize

2021 ◽  
Vol 12 ◽  
Author(s):  
Pedro M. P. Correia ◽  
Anabela Bernardes da Silva ◽  
Margarida Vaz ◽  
Elizabete Carmo-Silva ◽  
Jorge Marques da Silva
Keyword(s):  
High Temperature ◽  
Drought Stress ◽  
Heat Tolerance ◽  
Food Production ◽  
Carbon Fixation ◽  
Electron Transport Rate ◽  
Carbon Assimilation ◽  
Co2 Assimilation ◽  
Photosynthetic Performance

Increasing temperatures and extended drought episodes are among the major constraints affecting food production. Maize has a relatively high temperature optimum for photosynthesis compared to C3 crops, however, the response of this important C4 crop to the combination of heat and drought stress is poorly understood. Here, we hypothesized that resilience to high temperature combined with water deficit (WD) would require efficient regulation of the photosynthetic traits of maize, including the C4–CO2 concentrating mechanism (CCM). Two genotypes of maize with contrasting levels of drought and heat tolerance, B73 and P0023, were acclimatized at high temperature (38°C versus 25°C) under well-watered (WW) or WD conditions. The photosynthetic performance was evaluated by gas exchange and chlorophyll a fluorescence, and in vitro activities of key enzymes for carboxylation (phosphoenolpyruvate carboxylase), decarboxylation (NADP-malic enzyme), and carbon fixation (Rubisco). Both genotypes successfully acclimatized to the high temperature, although with different mechanisms: while B73 maintained the photosynthetic rates by increasing stomatal conductance (gs), P0023 maintained gs and showed limited transpiration. When WD was experienced in combination with high temperatures, limited transpiration allowed water-savings and acted as a drought stress avoidance mechanism. The photosynthetic efficiency in P0023 was sustained by higher phosphorylated PEPC and electron transport rate (ETR) near vascular tissues, supplying chemical energy for an effective CCM. These results suggest that the key traits for drought and heat tolerance in maize are limited transpiration rate, allied with a synchronized regulation of the carbon assimilation metabolism. These findings can be exploited in future breeding efforts aimed at improving maize resilience to climate change.

Flavones as a Privileged Scaffold in Drug Discovery: Current Developments

2019 ◽  
Vol 16 (7) ◽  
pp. 968-1001
Author(s):  
Pone K. Boniface ◽  
Ferreira I. Elizabeth
Keyword(s):  
Biological Activities ◽  
Therapeutic Agents ◽  
Pharmacological Properties ◽  
Chemical Transformations ◽  
National Library ◽  
Scientific Publications ◽  
Multifactorial Diseases ◽  
Naturally Occurring ◽  
Privileged Scaffold

Background: Flavones are one of the main subclasses of flavonoids with diverse pharmacological properties. They have been reported to possess antimalarial, antimicrobial, anti-tuberculosis, anti-allergic, antioxidant, anti-inflammatory activities, among others. Objective: The present review summarizes the recent information on the pharmacological properties of naturally occurring and synthetic flavones. Method: Scientific publications referring to natural and synthetic flavones in relation to their biological activities were hand-searched in databases such as SciFinder, PubMed (National Library of Medicine), Science Direct, Wiley, ACS, SciELO, Springer, among others. Results: As per the literature, seventy-five natural flavones were predicted as active compounds with reference to their IC50 (<20 µg/mL) in in vitro studies. Also, synthetic flavones were found active against several diseases. Conclusion: As per the literature, flavones are important sources for the potential treatment of multifactorial diseases. However, efforts toward the development of flavone-based therapeutic agents are still needed. The appearance of new catalysts and chemical transformations is expected to provide avenues for the synthesis of unexplored flavones, leading to the discovery of flavones with new properties and biological activities.

Sectioned rubisco crystals in TEM

1990 ◽  
Vol 48 (3) ◽  
pp. 664-665
Author(s):  
Gunnel Karlsson ◽  
Jan-Olov Bovin ◽  
Michael Bosma
Keyword(s):  
Plant Cell ◽  
Carbon Fixation ◽  
Unit Cell ◽  
Protein Crystals ◽  
Unit Cell Parameters ◽  
Cell Parameters ◽  
Photosynthetic Carbon Fixation ◽  
Photosynthetic Carbon

RuBisCO (D-ribulose-l,5-biphosphate carboxylase/oxygenase) is the most aboundant enzyme in the plant cell and it catalyses the key carboxylation reaction of photosynthetic carbon fixation, but also the competing oxygenase reaction of photorespiation. In vitro crystallized RuBisCO has been studied earlier but this investigation concerns in vivo existance of RuBisCO crystals in anthers and leaves ofsugarbeets. For the identification of in vivo protein crystals it is important to be able to determinethe unit cell of cytochemically identified crystals in the same image. In order to obtain the best combination of optimal contrast and resolution we have studied different staining and electron accelerating voltages. It is known that embedding and sectioning can cause deformation and obscure the unit cell parameters.

scholarly journals Assessment of Photo-Induced Cytotoxic Activity of Cachrys sicula and Cachrys libanotis Enriched-Coumarin Extracts against Human Melanoma Cells

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 123
Author(s):  
Mariangela Marrelli ◽  
Maria Rosaria Perri ◽  
Valentina Amodeo ◽  
Francesca Giordano ◽  
Giancarlo A. Statti ◽  
...  
Keyword(s):  
Phenolic Content ◽  
Melanoma Cells ◽  
Therapeutic Approaches ◽  
Qualitative And Quantitative ◽  
Aerial Parts ◽  
Naturally Occurring ◽  
Quantitative Analyses ◽  
Solid Liquid ◽  
Uva Radiation

Photochemotherapy is one of the most interesting current therapeutic approaches for the treatment of melanoma. Different classes of naturally occurring phytochemicals demonstrated interesting photoactive properties. The aim of this study was to evaluate the photocytotoxic potential of two Cachrys species from Southern Italy: C. sicula and C. libanotis (Apiaceae). The enriched-coumarin extracts were obtained from aerial parts through both traditional maceration and pressurized cyclic solid-liquid (PCSL) extraction using Naviglio extractor®. Qualitative and quantitative analyses of furanocoumarins were performed with GC-MS. The photocytotoxic effects were verified on C32 melanoma cells irradiated at a dose of 1.08 J/cm2. The apoptotic responses were also assessed. Moreover, phenolic content and the in vitro antioxidant potential were estimated. Xanthotoxin, bergapten, and isopimpinellin were identified. All the samples induced concentration-dependent photocytotoxic effects (IC50 ranging from 3.16 to 18.18 μg/mL). The C. libanotis sample obtained with Naviglio extractor® was the most effective one (IC50 = 3.16 ± 0.21 μg/mL), followed by C. sicula sample obtained with the same technique (IC50 = 8.83 ± 0.20 μg/mL). Both Cachrys samples obtained through PCSL induced up-regulation of apoptotic signals such as BAX (Bcl2-associated X protein) and PARP (poly ADP-ribose polymerase) cleavage. Moreover, these samples proved to be more photoactive, giving a greater upregulation of p21 protein in the presence of UVA radiation. Obtained results suggest that investigated species could be promising candidates for further investigations aimed to find new potential drugs for the photochemotherapy of skin cancer.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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