Control of sulfur metabolism

Although the pathways and regulation of sulfate uptake and assimilation are for most part understood at the physiological level, the molecular mechanisms of their regulation and the roles of multiple isoforms of key enzymes remain to be elucidated. For example, while plant responses to sulfate starvation are well described, the actual mechanisms of sulfur sensing and the associated signaling and transduction pathways are largely unknown. Understanding of such mechanisms of regulation is not only an intriguing biological question, but will also form a knowledge base essential to develop new strategies for improvement of nutrient use efficiency in crop plants. We have generated multiple resources that can now be utilised to address the following important questions:

• What are the mechanisms of sulfur homeostasis?

We are exploiting natural variation in accumulation of sulfate, nitrate, and phosphate for GWAS to identify genes contributing to nutrient homeostasis. Together with Olivier Loudet, David Salt, and Joe Jez we showed the importance of the key enzymes of sulfate assimilation ATP sulfurylase and APS reductase for control of sulfate levels. Through GWAS in Arabidopsis and Brassica napus we obtained a number of further candidate genes for such regulation and are analysing the mechanisms of their action. In addition, we are dissecting the mechanisms of regulation of the OAS cluster genes.

Key publications:

Kopriva S, Rahimzadeh Karvansara P, Takahashi H. (2024) Adaptive Modifications in Plant Sulfur Metabolism over Evolutionary Time. J Exp Bot. 75, 4697-4711

de Jager N, Shukla V, Koprivova A, Lyčka M, Bilalli L, You Y, Zeier J, Kopriva S, Ristova D. (2024) Traits linked to natural variation of sulfur content in A. thaliana leaf. J. Exp. Bot. 75, 1036-1050.

Zenzen I., Cassol D., Westhoff P., Kopriva S., Ristova D. (2024) Transcriptional and metabolic profiling of sulfur starvation response in two monocots. BMC Plant Biol, 24, 257.

Koprivova A., Elkatmis B., Gerlich S.C., Trick M., Harper A.L., Bancroft I., Kopriva S. (2023) Natural Variation in OASC Gene for Mitochondrial O-Acetylserine Thiollyase Affects Sulfate Levels in Arabidopsis. Plants 12, 35.

Rahimzadeh Karvansara P., Kelly C., Krone R., Zenzen I., Ristova D., Silz E., Jobe T.O., Kopriva S. (2023) Unique features of regulation of sulfate assimilation in monocots. J. Exp. Bot. 74, 308-320.

Pavlů J., Kerchev P., Černý M., Novák J., Berka M., Jobe T.O., López Ramos J.M., Saiz-Fernández I., Rashotte A.M., Kopriva S., Brzobohatý B. (2022) Cytokinin modulates sulfur and glutathione metabolic network. J. Exp. Bot. 73, 7417-7433.

Courbet G., D’Oria A., Lornac A., Diquélou S., Pluchon S., Arkoun S., Koprivova A., Kopriva S., Etienne P., Ourry A. (2021) Specificity and Plasticity of the Functional Ionome of Brassica napus and Triticum aestivum Subjected to Macronutrient Deprivation. Front. Plant Sci. 12, 641648.

Giovannetti M., Göschl C., Dietzen C., Andersen S.U., Kopriva S., Busch W. (2019) Identification of novel genes involved in phosphate accumulation in Lotus japonicus through Genome Wide Association mapping of root system architecture and anion content. PLoS Genet. 15, e1008126.

Maillard A., Sorin E., Etienne P., Diquelou S., Koprivova A., Kopriva S., Arkoun M., Gallardo K., Turner M., Cruz F., Yvin J.-C., Ourry A. (2016) Non-Specific Root Transport of Nutrient Gives Access to an Early Nutritional Indicator: The Case of Sulfate and Molybdate. PLoS One 11, e0166910.

Huang X.-Y., Chao D.-Y., Koprivova A., Danku J., Wirtz M., Müller S., Sandoval F.J., Bauwe H., Roje S., Dilkes B., Hell R., Kopriva S., Salt D.E. (2016) Nuclear localised MORE SULPHUR ACCUMULATION1 epigenetically regulates sulphur homeostasis in Arabidopsis thaliana. PLoS Genet. 12, e100627.

Chao D.-Y., Baraniecka P., Danku J., Koprivova A., Lahner B., Luo H., Yakubova E., Kopriva S., Salt D.E. (2014) Naturally occurring isoforms of the key sulfur assimilation enzyme APR2 vary in catalytic capacity across the Arabidopsis thaliana species range. Plant Physiol. 166, 1450-1462

Koprivova A., Harper A.L., Trick M., Bancroft I., Kopriva S. (2014) Dissection of control of anion homeostasis by Associative Transcriptomics in Brassica napus. Plant Physiol., 166, 442-450.

Herrmann J., Ravilious G.E., McKinney S.E., Westfall C.S., Lee S.G., Baraniecka P., Giovannetti M., Kopriva S., Krishnan H.B., Jez J.M. (2014) Structure and Mechanism of Soybean ATP Sulfurylase and the Committed Step in Plant Sulfur Assimilation. J. Biol. Chem. 289, 10919-10929.

Koprivova A., Giovannetti M., Baraniecka P., Lee B.-R., Grondin C., Loudet O., Kopriva S. (2013) Natural Variation in ATPS1 Isoform of ATP Sulfurylase Contributes to Control of Sulfate Levels in Arabidopsis. Plant Physiol. 163, 1133-1141

Loudet O., Saliba-Colombani V., Camilleri C., Calenge F., Gaudon V., Koprivova A., North K.A., Kopriva S., Daniel-Vedele F. (2007) Natural variation for sulfate content in Arabidopsis is highly controlled by adenosine 5'-phosphosulfate reductase. Nat. Genet. 39, 896-900
 

• How is partitioning of sulphur between primary and secondary metabolism regulated?

Secondary metabolites represent an important sink for nutrients but have also essential functions for plant stress defense. The plant thus has to balance the primary and secondary metabolism to achieve optimal growth at diverse environmental conditions. We identified APS kinase as major determinant of sulfur partitioning between primary and secondary metabolism and found coordinate regulation of genes of primary S assimilation with genes of glucosinolate biosynthesis network. We found new components of the network linking primary and secondary sulfur metabolism, such as the FIERY1. However, many questions on the importance of the subcellular distribution of the metabolites and pathway enzymes still remain open, such as the role of redox regulation, as well as the nature and function of the necessary transporters. Even more intriguing is the role of APS kinase in plant species that do not form the sulfated secondary compounds, glucosinolates.

Key publications:

Ashykhmina A., Chan K.X., Frerigmann H., Van Breusegem F., Kopriva S., Flügge U.-I., Gigolashvili T. (2022) Dissecting the role of SAL1 in metabolising the stress signalling molecule 3´-phosphoadenosine 5´-phosphate in different cell compartments. Front. Mol. Biosci. 8, 763795.

Ashykhmina N., Lorenz M., Frerigmann H., Koprivova A., Hofsetz E., Stührwohldt N., Flügge U.-I., Haferkamp I-, Kopriva S., Gigolashvili T. (2019) PAPST2 plays a critical role for PAP removal from the cytosol and subsequent 1 degradation in plastids and mitochondria. Plant Cell 31, 231-249.

Chan K.X., Mabbitt P.D., Phua S.Y., Mueller J.W., Nisar N., Gigolashvili T., Stroeher E., Grassl J., Arlt W., Estavillo G.M., Jackson C.J., Pogson B.J. (2016) Sensing and signaling of oxidative stress in chloroplasts by inactivation of the SAL1 phosphoadenosine phosphatase.  Proc Natl Acad Sci U S A 113, E4567-4576.

Huseby S., Koprivova A., Lee B.-R., Saha S., Mithen R., Wold A.-B., Bengtsson G.B., Kopriva S. (2013) Diurnal and light regulation of sulfur assimilation and glucosinolate biosynthesis in Arabidopsis. J. Exp. Bot. 64, 1039-1048

Gigolashvili T., Geier M., Ashykhmina N., Frerigmann H., Wulfert S., Krüger S., Mugford S.G., Kopriva S., Haferkamp I., Flügge U.-I. (2012) Much more than a thylakoid ADP/ATP carrier - Enlightening a role of TAAC in plastidic phosphoadenosine 5‘-phosphosulfate (PAPS) supply to the cytosol. Plant Cell 24, 4187-4204

Lee B.-R., Huseby S., Koprivova A., Chételat A., Wirtz M., Mugford S.T., Navid E., Brearley C., Saha S., Mithen R., Hell R., Farmer E.E., Kopriva S. (2012) Effects of fou8/fry1 mutation on sulfur metabolism. Is decreased internal sulfate the trigger of sulfate starvation response? PLoS ONE 7, e39425

Mugford S.G., Lee B.-R., Koprivova A., Matthewman C., Kopriva S. (2011) Control of sulfur partitioning between primary and secondary metabolism. Plant J. 65, 96-105.

Yatusevich R., Mugford S.G., Matthewman C., Gigolashvili T., Frerigmann H., Delaney S., Koprivova A., Flügge U.-I., Kopriva S. (2010) Genes of primary sulfate assimilation are part of the glucosinolate biosynthetic network in Arabidopsis thaliana. Plant J. 62, 1-11.

Mugford S.G., Matthewman C.A., Hill L., Kopriva S. (2010) Adenosine 5’ phosphosulfate kinase is essential for Arabidopsis viability. FEBS Lett. 584, 119-123

Kopriva S., Mugford S.G., Matthewman C.A., Koprivova A. (2009) Plant sulfate assimilation genes: redundancy vs. specialization. Plant Cell Rep. 28, 1769-1780.

Mugford S.G., Yoshimoto N., Reichelt M., Wirtz M., Hill L., Mugford S.T., Nakazato Y., Noji M., Takahashi H., Kramell R., Gigolashvili T., Flügge U.-I., Wasternack C., Gershenzon J., Hell R., Saito K., Kopriva S. (2009) Disruption of Adenosine-5’-Phosphosulphate Kinase in Arabidopsis Reduces Levels of Sulphated Secondary Metabolites. Plant Cell 21, 910-927.
 

• What is the role of ethylene signaling in control of sulfur nutrition?

The interaction of ethylene signaling and sulfur metabolism has been demonstrated on several levels, but the mechanistic understanding is only fragmented, despite the close connection of ethylene synthesis and sulfur metabolism, through the SAM and methionine salvage cycle. For example, we showed previously that APS reductase is up-regulated by ethylene and its regulation by salt stress is disrupted in ethylene signaling mutants. More significant is, however, that the key regulator of sulfate starvation response SLIM1 is a member of the EIN3-like family of transcription factors. Interestingly, also EIL2 has been implicated in regulation of some parts of the sulfate starvation response in tobacco and many sulfur related genes have been found among genes regulated by EIN3. In addition, in our search for genes underlying variation in nutrient homeostasis we identified two genes of ethylene signaling, EIN2 and EIN5, associated with variation in sulfate and phosphate levels in Brassica napus. Thus, ethylene signaling might be important not only for regulating the SLIM1 mediated response of the sulfate assimilation pathway and the control of sulfur metabolite pools, such as glucosinolates, but also for nutrient homeostasis during the normal life cycle. We are addressing the connection by detailed analyses of EIL genes in Arabidopsis as well as a range of mutants in ethylene signaling.

Key publications:

Ristova D., Kopriva S. (2022) Sulfur in Plants, lessons from Arabidopsis: from signaling to starvation response and interactions. iScience in press

Dietzen C., Koprivova A., Whitcomb S.J., Langen G., Jobe T.O., Hoefgen R., Kopriva S. (2020) The transcription factor EIL1 participates in the regulation of sulfur deficiency response in Arabidopsis. Plant Physiol 184, 2120-2136.

Koprivova A., Kopriva S. (2016) Hormonal control of sulfate uptake and assimilation. Plant Mol. Biol. 91, 617-627.

Dietzen C. (2016) Arabidopsis EIL1 Regulates the Plants Sulfur Response and Metabolism in Absence of SLIM1. MSc Thesis University of Cologne.