Engineering a highly sensitive biosensor for abscisic acid in mammalian cells

Kim, Seo Woo; Alci, Kübra; Gaever, F. Van; Driege, Yasmine; Bicalho, Keylla; Goeminne, Geert; Libert, Claude; Goossens, Alain; Beyaert, Rudi; Staal, Jens

doi:10.1002/1873-3468.14431

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…This design solely relies on the ABA-induced dimerization and does not require a functional phosphatase. In a recent study, a highly sensitive ABA biosensor for use in mammalian cells was developed based on the same design principle (Kim et al, 2022). In addition, two latest studies changed the ligand specificity of PYR/PYL receptors and developed PYR/PYL-PP2C-based biosensors for various non-native ligands, including herbicides, cannabinoids and organophosphates (Beltrán et al, 2022;Zimran et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Sense and Screen-ability: Development of tuneable, biosensor-based screening platforms for abscisic acid

Otto

Dabirian

David

et al. 2023

Preprint

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The activities of heterologous enzymes often limit the production titers, rates and yields of cell factories. With the help of biosensors, large random mutagenesis libraries can be screened for improved enzyme variants in a high-throughput manner, even if the enzyme-of-interest is poorly characterised. We previously constructed a Saccharomyces cerevisiae cell factory for the heterologous production of abscisic acid (ABA), a high-value product with a broad range of applications in medicine, agriculture and nutrition. In the current study, we developed high-throughput screening platform strains for two rate-limiting cytochrome P450 monooxygenases, BcABA1 and BcABA2, in the ABA biosynthetic pathway. The screening platforms are designed to minimize the occurrence of false positives during screening experiments. We thoroughly characterised two plant protein-based ABA biosensor candidates. Furthermore, we designed a simple genetic switch, based on the thiamine-repressible promoter pTHI4, to regulate the expression level of enzyme variants. We demonstrated that ABA production can be fine-tuned by varying thiamine concentration in the media. In-depth analysis of the platform strains revealed that screening conditions can be optimized by varying thiamine concentration and cultivation time, making it possible to utilize the full dynamic and operational range of the biosensor. In the future, the constructed strains can be used to screen for improved BcABA1 and BcABA2 variants.

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Section: Introductionmentioning

confidence: 99%

Sense and Screen-ability: Development of tuneable, biosensor-based screening platforms for abscisic acid

Otto

Dabirian

David

et al. 2023

Preprint

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Progress and limitations in engineering cellular adhesion for research and therapeutics

Chao,

Zukin,

Fortuna

et al. 2024

Trends in Cell Biology

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The phytohormone abscisic acid enhances remyelination in mouse models of multiple sclerosis

Van Gaever,

Mingneau,

Vanherle

et al. 2024

Front. Immunol.

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IntroductionOver the past few decades, there has been a sudden rise in the incidence of Multiple Sclerosis (MS) in Western countries. However, current treatments often show limited efficacy in certain patients and are associated with adverse effects, which highlights the need for safer and more effective therapeutic approaches. Environmental factors, particularly dietary habits, have been observed to play a substantial role in the development of MS. In this study, we are the first to investigate the potential protective effect of the phytohormone abscisic acid (ABA) in MS. ABA, which is abundant in fruits such as figs, apricots and bilberries, is known to cross the blood-brain barrier and has demonstrated neuroprotective effects in conditions like depression and Alzheimer's disease.MethodsIn this study, we investigated whether ABA supplementation enhances remyelination in both ex vivo and in vivo mouse models.ResultsOur results indicated that ABA enhanced remyelination and that this enhanced remyelination is associated with increased lipid droplet load, reduced levels of degraded myelin, and a higher abundance of F4/80+ cells in the demyelinated brain of mice treated with ABA. In in vitro models, we further demonstrated that ABA treatment elevates lipid droplet formation by enhancing the phagocytic capacity of macrophages. Additionally, in a mouse model of microglial activation, we showed that ABA-treated mice maintain a less inflammatory microglial phenotype.ConclusionOur findings highlight a crucial role for macrophages and microglia in enabling ABA to enhance the remyelination process. Furthermore, ABA’s ability to improve remyelination together with its ability to reduce microglial activation, make ABA a promising candidate for modulating macrophage phenotype and reducing neuroinflammation in MS.

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Engineering a highly sensitive biosensor for abscisic acid in mammalian cells

Cited by 3 publications

References 57 publications

Sense and Screen-ability: Development of tuneable, biosensor-based screening platforms for abscisic acid

Sense and Screen-ability: Development of tuneable, biosensor-based screening platforms for abscisic acid

Progress and limitations in engineering cellular adhesion for research and therapeutics

The phytohormone abscisic acid enhances remyelination in mouse models of multiple sclerosis

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