The Abiotic Oxidation of Organic Acids to Malonate

Rice, Gavin; Reddy, Y. Jayasudhan; Krishnamurthy, Ramanarayanan; Springsteen, Greg

doi:10.1055/s-0036-1588649

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…The decreased abundance of these Trp products combined with the reduction in browning and ammonia production to below the no Trp control level suggests that aKG may be protecting multiple CCM components from degradation via an antioxidant function. Not much is known about the function of aKG as an antioxidant, although it is known that the reaction with the oxidant hydrogen peroxide causes the oxidative decarboxylation of the aketoacid, forming succinic acid (66) [42]. The feature corresponding to this compound was detected in the feed in negative mode (Figure 7D), and the abundance was increased in the feed+aKG condition, supporting the hypothesis that aKG is functioning as an antioxidant.…”

Section: Inhibition Of Browning and Degradation Product Formation Using Alpha-ketoglutaric Acidmentioning

confidence: 65%

Degradation Products of Tryptophan in Cell Culture Media: Contribution to Color and Toxicity

Schnellbaecher

Lindig

Mignon

et al. 2021

IJMS

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Biomanufacturing processes may be optimized by storing cell culture media at room temperature, but this is currently limited by their instability and change in color upon long-term storage. This study demonstrates that one of the critical contributing factors toward media browning is tryptophan. LC-MS technology was utilized to identify tryptophan degradation products, which are likely formed primarily from oxidation reactions. Several of the identified compounds were shown to contribute significantly to color in solutions but also to exhibit toxicity against CHO cells. A cell-culture-compatible antioxidant, a-ketoglutaric acid, was found to be an efficient cell culture media additive for stabilizing components against degradation, inhibiting the browning of media formulations, and decreasing ammonia production, thus providing a viable method for developing room-temperature stable cell culture media.

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Section: Inhibition Of Browning and Degradation Product Formation Using Alpha-ketoglutaric Acidmentioning

confidence: 65%

Degradation Products of Tryptophan in Cell Culture Media: Contribution to Color and Toxicity

Schnellbaecher

Lindig

Mignon

et al. 2021

IJMS

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“…One way to achieve this is to treat the mixture of products of the reductive-glyoxylate pathway with prebiotically available H2O2, 43 which will convert them to malonate as the final product. 7 Then, in principle, the sequence of reactions can be restarted by adding fresh glyoxylate to the same pot (Fig. 5B).…”

mentioning

confidence: 99%

“…46 Lastly, the chemistry outlined here depends on the prebiotic availability of glyoxylate and malonate for which there is some support. [4][5][6][7]47 It is plausible that as the experimental demonstration grows for the central role of glyoxylate and malonate chemistry, it will spur more efforts to put constraints on their prebiotic provenance.…”

mentioning

confidence: 99%

Cyanide as a Primordial Reductant enables a Protometabolic Reductive Glyoxylate Pathway

Krishnamurthy

Yadav

Pulletikurti

et al. 2021

Preprint

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Investigation of prebiotic chemical pathways leading to protometabolic forerunners of metabolism has been largely based on bio-inspired (iron-mediated) reductive conversion of carbon dioxide and of carboxylic acid substrates.1,2 While attractive from a parsimony point of view, this approach has been challenging with debatable outcomes.3,4 Herein, we show that cyanide reacts with citric acid cycle (TCA) intermediates and derivatives and acts as a primordial reducing agent mediating abiotic reductive transformations. The hydrolysis of the cyanide adducts followed by decarboxylation enables the efficient reductive-decarboxylative transformation of oxaloacetate to malate and fumarate to succinate while pyruvate and α-ketoglutarate are not reduced. In the presence of glyoxylate,5,6 malonate7 and malononitrile,8 alternative pathways emerge, which after decarboxylation produce metabolic intermediates and related compounds also found in meteorites.9 These results, along with the previous demonstration of the metal-free alpha-keto analog of the reverse-TCA cycle,4,6 suggest that (a) alternative paradigms of cyanide-based protometabolic reactions bypassing the abiotic reductive-carboxylation steps can be prebiotically viable, (b) a novel reductive glyoxylate pathway can be a precursor to the r-TCA cycle and (c) the type of sophisticated carboxylation and reduction chemistries which are part of extant metabolic cycles10,11 are an evolutionary invention mediated by complex metalloproteins11.

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Nonenzymatic Metabolic Reactions and Life’s Origins

2020

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Prebiotic chemistry aims to explain how the biochemistry of life as we know it came to be. Most efforts in this area have focused on provisioning compounds of importance to life by multi-step synthetic routes that do not resemble biochemistry. However, gaining insight into why core metabolism uses the molecules, reactions, pathways, and overall organization that it does requires us to consider molecules not only as synthetic end goals. Equally important are the dynamic processes that build them up and break them down. This perspective has led many researchers to the hypothesis that the first stage of the origin of life began with the onset of a primitive non-enzymatic version of metabolism, initially catalyzed by naturally occurring minerals and metal ions. This view of life's origins has come to be known as "metabolism first". Continuity with modern metabolism would require a primitive version of metabolism to build and break down ketoacids, sugars, amino acids, and ribonucleotides in much the same way as the pathways that do it today. This review discusses metabolic pathways of relevance to the origin of life in a manner accessible to chemists, and summarizes experiments suggesting several pathways might have their roots in prebiotic chemistry. Finally, key remaining milestones for the protometabolic hypothesis are highlighted.

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The Abiotic Oxidation of Organic Acids to Malonate

Cited by 5 publications

References 38 publications

Degradation Products of Tryptophan in Cell Culture Media: Contribution to Color and Toxicity

Degradation Products of Tryptophan in Cell Culture Media: Contribution to Color and Toxicity

Cyanide as a Primordial Reductant enables a Protometabolic Reductive Glyoxylate Pathway

Nonenzymatic Metabolic Reactions and Life’s Origins

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