1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Hauryliuk, V., Atkinson, G. C., Murakami, K. S., Tenson, T. & Gerdes, K.
Recent functional insights into the role of (p)ppGpp in bacterial physiology.
Nat. Rev. Microbiol. 13, 298–309 (2015).
Potrykus, K. & Cashel, M. (p)ppGpp: still magical? Annu. Rev. Microbiol. 62,
35–51 (2008).
Srivatsan, A. & Wang, J. D. Control of bacterial transcription, translation and
replication by (p)ppGpp. Curr. Opin. Microbiol. 11, 100–105 (2008).
Kanjee, U., Ogata, K. & Houry, W. A. Direct binding targets of the stringent
response alarmone (p)ppGpp. Mol. Microbiol. 85, 1029–1043 (2012).
Cashel, M. & Gallant, J. Two compounds implicated in the function of the RC
gene of Escherichia coli. Nature 221, 838–841 (1969).
Laffler, T. & Gallant, J. spoT, a new genetic locus involved in the stringent
response in E. coli. Cell 1, 27–30 (1974).
Atkinson, G. C., Tenson, T. & Hauryliuk, V. The RelA/SpoT Homolog (RSH)
Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and
Hydrolases across the Tree of Life. Plos One 6, e23479 (2011).
Akinyanju, J. & Smith, R. J. Accumulation of ppGpp and pppGpp during
nitrogen deprivation of the cyanophyte Anabaena cylindrica. FEBS lett. 107,
173–176 (1979).
Friga, G., Borbely, G. & Farkas, G. L. Accumulation of guanosine
tetraphosphate (ppGpp) under nitrogen starvation in Anacystis nidulans, a
cyanobacterium. Arch. Microbiol. 129, 341–343 (1981).
Doolittle, W. F. The cyanobacterial genome, its expression, and the control of
that expression. Adv. Microb. Physiol. 20, 1–102 (1980).
Surányi, G., Korcz, A., Pálfi, Z. & Borbély, G. Effects of light deprivation on
RNA synthesis, accumulation of guanosine 3’(2’)-diphosphate 5’-diphosphate,
and protein synthesis in heat-shocked Synechococcus sp. strain PCC 6301, a
cyanobacterium. J. Bacteriol. 169, 632–639 (1987).
Akinyanju, J. & Smith, R. J. The accumulation of phosphorylated guanosine
nucleotides in Anabaena cylindrica. N. Phytol. 105, 117–122 (1987).
Zhang, S. R., Lin, G. M., Chen, W. L., Wang, L. & Zhang, C. C. ppGpp
metabolism is involved in heterocyst development in the cyanobacterium
Anabaena sp. strain PCC 7120. J. Bacteriol. 195, 4536–4544 (2013).
Diamond, S., Jun, D., Rubin, B. E. & Golden, S. S. The circadian oscillator in
Synechococcus elongatus controls metabolite partitioning during diurnal
growth. Proc. Natl Acad. Sci. USA 112, E1916–E1925 (2015).
van der Biezen, E. A., Sun, J., Coleman, M. J., Bibb, M. J. & Jones, J. D.
Arabidopsis RelA/SpoT homologs implicate (p)ppGpp in plant signaling. Proc.
Natl Acad. Sci. USA 97, 3747–3752 (2000).
Takahashi, K., Kasai, K. & Ochi, K. Identification of the bacterial alarmone
guanosine 5′-diphosphate 3′-diphosphate (ppGpp) in plants. Proc. Natl Acad.
Sci. USA 101, 4320–4324 (2004).
Maekawa, M. et al. Impact of the plastidial stringent response in plant growth
and stress responses. Nat. Plants 1, 15167 (2015).
Hood, R. D., Higgins, S. A., Flamholz, A., Nichols, R. J. & Savage, D. F. The
stringent response regulates adaptation to darkness in the cyanobacterium
Synechococcus elongatus. Proc. Natl Acad. Sci. USA 113, E4867–E4876 (2016).
Puszynska, A. M. & O’Shea, E. K. ppGpp Controls Global Gene Expression
in Light and in Darkness in S. elongatus. Cell Rep. 21, 3155–3165 (2017).
Nanamiya, H. et al. Identification and functional analysis of novel (p)ppGpp
synthetase genes in Bacillus subtilis. Mol. Microbiol. 67, 291–304 (2008).
Llop, A. et al. Pleiotropic effects of PipX, PipY, or RelQ overexpression on
growth, cell size, photosynthesis, and polyphosphate accumulation in the
cyanobacterium Synechococcus elongatus PCC7942. Front. Microbiol. 14,
1141775 (2023).
COMMUNICATIONS BIOLOGY | (2023)6:1285 | https://doi.org/10.1038/s42003-023-05632-1 | www.nature.com/commsbio
11
ARTICLE
COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-023-05632-1
22. García-Domínguez, M., Reyes, J. C. & Florencio, F. J. NtcA represses
transcription of gifA and gifB, genes that encode inhibitors of glutamine
synthetase type I from Synechocystis sp. PCC 6803. Mol. Microbiol 35,
1192–1201 (2000).
23. Giner-Lamia, J. et al. Identification of the direct regulon of NtcA during early
acclimation to nitrogen starvation in the cyanobacterium Synechocystis sp.
PCC 6803. Nucleic Acid Res. 45, 11800–11820 (2017).
24. Muro-Pastor, M. I., Reyes, J. C. & Florencio, F. J. Cyanobacteria perceive
nitrogen status by sensing intracellular 2-oxoglutarate levels. J. Biol. Chem.
276, 38320–38328 (2001).
25. Forchhammer, K. & Selim, K. A. Carbon/nitrogen homeostasis control in
cyanobacteria. FEMS Microbiol. Rev. 44, 33–53 (2020).
26. Forchhammer, K. & Schwarz, R. Nitrogen chlorosis in unicellular
cyanobacteria – a developmental program for surviving nitrogen deprivation.
Environ. Microbiol. 21, 1173–1184 (2019).
27. Laurent, S. et al. Nonmetabolizable analogue of 2-oxoglutarate elicits
heterocyst differentiation under repressive conditions in Anabaena sp. PCC
7120. Proc. Natl Acad. Sci. USA 102, 9907–9912 (2005).
28. Luque, I., Zabulon, G., Contreras, A. & Houmard, J. Convergence of two
global transcriptional regulators on nitrogen induction of the stressacclimation gene nblA in the cyanobacterium Synechococcus sp. PCC 7942.
Mol. Microbiol. 41, 937–947 (2001).
29. Espinosa, J. et al. PipX, the coactivator of NtcA, is a global regulator in
cyanobacteria. Proc. Natl Acad. Sci. USA 111, E2423–E2430 (2014).
30. Zhao, M. X. et al. Structural basis for the allosteric control of the global
transcription factor NtcA by the nitrogen starvation signal 2-oxoglutarate.
Proc. Natl Acad. Sci. USA 107, 12487–12492 (2010).
31. Llácer, J. L. et al. Structural basis for the regulation of NtcA-dependent
transcription by proteins PipX and PII. Proc. Natl Acad. Sci. USA 107,
15397–15402 (2010).
32. Hasunuma, T. et al. Dynamic metabolic profiling of cyanobacterial glycogen
biosynthesis under conditions of nitrate depletion. J. Exp. Bot. 64, 2943–2954
(2013).
33. Meeks, J. C. et al. The pathways of assimilation of 13NH4+ by the
cyanobacterium, Anabaena cylindrica. J. Biol. Chem. 252, 7894–7900 (1977).
34. Isabel Muro-Pastor, M., Reyes, J. C. & Florencio, F. J. Ammonium assimilation
in cyanobacteria. Photosyn. Res. 83, 135–150 (2005).
35. Hasunuma, T. et al. Metabolic turnover analysis by a combination of in vivo
13C-labelling from 13CO and metabolic profiling with CE-MS/MS reveals
rate-limiting steps of the C3 photosynthetic pathway in Nicotiana tabacum
leaves. J. Exp. Bot. 61, 1041–1051 (2010).
36. Nishii, M., Ito, S., Katayama, N. & Osanai, T. Biochemical elucidation of
citrate accumulation in Synechocystis sp. PCC 6803 via kinetic analysis of
aconitase. Sci. Rep. 11, 17131 (2021).
37. Lancien, M., Gadal, P. & Hodges, M. Enzyme redundancy and the importance
of 2-oxoglutarate in higher plant ammonium assimilation. Plant Physiol. 123,
817–824 (2000).
38. Tanaka, K. et al. Dark accumulation of downstream glycolytic intermediates
initiates robust photosynthesis in cyanobacteria. Plant Physiol. 191,
2400–2413 (2023).
39. Zhang, Y., Zborníková, E., Rejman, D. & Gerdes, K. Novel (p)ppGpp Binding
and Metabolizing Proteins of Escherichia coli. mBio 9, e02188–17 (2018).
40. Wang, B. et al. Affinity-based capture and identification of protein effectors of
the growth regulator ppGpp. Nat. Chem. Biol. 15, 141–150 (2019).
41. Görl, M., Sauer, J., Baier, T. & Forchhammer, K. Nitrogen-starvation-induced
chlorosis in Synechococcus PCC 7942: adaptation to long-term survival.
Microbiology 144, 2449–2458 (1998).
42. Zilliges, Y. Glycogen, a dynamic cellular sink and reservoir for carbon.
Herrero, A. (Ed.), The Cell Biology of Cyanobacteria, Caister Academic Press,
189–210 (2014).
43. Cano, M. et al. Glycogen Synthesis and Metabolite Overflow Contribute to
Energy Balancing in Cyanobacteria. Cell Rep. 23, 667–672 (2018).
44. Carrieri, D., Paddock, T., Maness, P.-C., Seibert, M. & Yu, J. Photo-catalytic
conversion of carbon dioxide to organic acids by a recombinant
cyanobacterium incapable of glycogen storage. Energy Environ. Sci. 5,
9457–9461 (2012).
45. Klotz, A., Reinhold, E., Doello, S. & Forchhammer, K. Nitrogen Starvation
Acclimation in Synechococcus elongatus: Redox-Control and the Role of
Nitrate Reduction as an Electron Sink. Life (Basel) 5, 888–904 (2015).
46. Karradt, A., Sobanski, J., Mattow, J., Lockau, W. & Baier, K. NblA, a key
protein of phycobilisome degradation, interacts with ClpC, a HSP100
chaperone partner of a cyanobacterial Clp. protease J. Biol. Chem. 283,
32394–32403 (2008).
47. Pernil, R., Picossi, S., Herrero, A., Flores, E. & Mariscal, V. Amino Acid
Transporters and Release of Hydrophobic Amino Acids in the HeterocystForming Cyanobacterium Anabaena sp. Strain PCC 7120. Life (Basel) 5,
1282–1300 (2015).
12
48. Iyer, S., Le, D., Park, R. & Kim, M. Distinct mechanisms coordinate
transcription and translation under carbon and nitrogen starvation in
Escherichia coli. Nat. Microbiol. 3, 741–748 (2018).
49. Hasunuma, T. et al. Overexpression of flv3 improves photosynthesis in the
cyanobacterium Synechocystis sp. PCC6803 by enhancement of alternative
electron flow. Biotechnol. Biofuels 7, 493 (2014).
50. Allen, M. M. & Stanier, R. Y. Growth and division of some unicellular bluegreen algae. J. Gen. Microbiol. 51, 199–202 (1968).
51. Watanabe, S. et al. Light-dependent and asynchronous replication of
cyanobacterial multi-copy chromosomes. Mol. Microbiol. 83, 856–865 (2012).
52. Clerico, E. M., Ditty, J. L. & Golden, S. S. Specialized techniques for sitedirected mutagenesis in cyanobacteria. Rosato, E. (Ed.), Circadian rhythms.
Methods Mol. BiolTM. 362, Humana Press, 155–171 (2007).
53. Wagner, G. P., Kin, K. & Lych, V. J. Measurement of mRNA abundance using
RNA-seq data: RPKM measure is inconsistent among samples. Theory Biosci.
131, 281–285 (2012).
54. Beinert, H., Kennedy, M. C. & Stout, C. D. Aconitase as Iron−Sulfur Protein,
Enzyme, and Iron-Regulatory Protein. Chem. Rev. 96, 2335–2374 (1996).
55. Bradford, M. M. A rapid and sensitive method for the quantitation of
microgram quantities of protein utilizing the principle of protein-dye binding.
Anal. Biochem. 72, 248–254 (1976).
56. Collos, Y. et al. An optical method for the rapid measurement of micromolar
concentrations of nitrate in marine phytoplankton cultures. J. Appl. Phycol.
11, 179–184 (1999).
Acknowledgements
The authors thank Ms. Hiroko Koizumi for their technical assistance. The RNA
sequencing was performed by Research Institute of Green Science and Technology,
Shizuoka University. This work was supported by Japan Science and Technology Agency
(JST)-Mirai Program Grant Number JPMJMI19E4, the Ministry of Education, Culture,
Sports, Science, and Technology (MEXT), Japan.
Author contributions
R.H. and R.O. contributed equally. R.O., H.A., and T.H. conceived and designed the research.
R.H., R.O., M.M, and Y.K. performed most experiments and M.M. conducted CE-TOFMS
analysis. S.I. and K.T. contributed to the interpretation of the results. R.H., R.O., Y.K., H.A., and
T.H. analyzed data. A.K. and T.H. supervised the research. R.H., Y.K., R.O., H.A., and T.H.
wrote the manuscript. All authors approved the final version of the manuscript.
Competing interests
The authors declare no competing interests.
Additional information
Supplementary information The online version contains supplementary material
available at https://doi.org/10.1038/s42003-023-05632-1.
Correspondence and requests for materials should be addressed to Tomohisa
Hasunuma.
Peer review information Communications Biology thanks Cheng-Cai Zhang, Karl
Forchhammer and the other, anonymous, reviewer(s) for their contribution to the peer
review of this work. Primary Handling Editors: Haichun Gao and David Favero. A peer
review file is available.
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