Plants, as sessile organisms, frequently suffer from deleterious environmental stimuli. Many cellular metabolic processes, such as carbohydrates, amino acids, lipids, and energy metabolism, are influenced by different developmental stages and abiotic stresses (Van Zelm et al., 2020; Mansour and Hassan, 2022). In response to developmental changes and external challenges, plants have evolved sophisticated mechanisms to better suit plant growth and environmental changes by integrating their internal metabolic status and optimizing metabolic reprogramming. One of these metabolic processes is the so-called hexosamine biosynthesis pathway (HBP), which utilizes fructose-6-phosphate (Fru-6-P), glutamine, acetyl-coenzyme A (acetyl-CoA), and uridine triphosphate (UTP) as substrates to synthesize uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) ( Figure 1 ). As the metabolic flux through HBP integrates glycolysis, amino acid, lipid, and nucleic acid pathways to maintain their balance and keep UDP-GlcNAc homeostasis, HBP may function as a metabolic integrator or hub for sensing nutrients (Buse, 2006; Chiaradonna et al., 2018) to link cellular nutrients/or energy signals and external cues. The HBP flux that generates UDP-GlcNAc is primarily regulated by the rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase (GFAT) activity and the obligatory substrate of O-linked GlcNAc transferase (OGT). The increased flux through HBP might be linked to insulin resistance, the vascular complications of diabetes, and cancer formation in mammals (Buse, 2006; Chiaradonna et al., 2018).

UDP-GlcNAc, the active form of GlcNAc, is a fundamental amino sugar moiety essential for the glycosylation of proteins and lipids (Ebert et al., 2018), glycosylphosphatidylinositol (GPI)-anchor proteins (Lalanne et al., 2004), a cell wall component of chitin in yeast, and an exoskeleton of arthropods (Maia, 1994; Kato et al., 2002; Arakane et al., 2011). UDP-GlcNAc is synthesized through an HBP that involves four consecutive reactions orderly catalyzed by a GFAT (Hassid et al., 1959; Durand et al., 2008), a glucosamine-6-P N-acetyltransferase (GNA) (Vetting et al., 2005; Wang et al., 2008a), an N-acetylglucosamine-phosphate mutase (AGM)/or phosphoacetylglucosamine mutase (Mio et al., 2000), and an N-acetylglucosmine-1-P-uridylyltransferase (GlcNAc1pUT, Yang et al., 2010) or a UDP-N-acetylglucosamine pyrophosphorylase (UAP; Wang et al., 2015, Wang et al., 2021). These processes are essential for cell growth and stress response and are conserved across organisms (Milewski et al., 2006). Dysfunction of HBP enzymes frequently causes severe phenotypes (Schimmelpfeng et al., 2006); moreover, a complete block of HBP normally results in lethality in yeast, mammals, and plants (Milewski et al., 2006; Chen et al., 2014; Pantaleon, 2015; Vu et al., 2019; Jia et al., 2023).

In the past, the function and regulation of HBP have been more intensively studied in microbes and mammals than in plants. The application of HBP products or intermediates through dietary treatment has been proposed as a therapy for human genetic disorders (Paneque et al., 2023). Elegant reviews have been recently reported on the function and regulation of HBP, which are primarily stressed in microbes (Wyllie et al., 2022) and eukaryotes of mammals (Paneque et al., 2023); however, an overview of HBP functions in plants is lacking. As research progress has greatly advanced in plant HBP study in recent years, in this review, we update our current knowledge of HBP function in plants and its stress responses. In addition, we provide an overview of the salvage pathway of HBP and the targets of UDP-GlcNAc in two major co- or post-translational modifications, N-linked glycosylation (N-glycosylation) and O-linked β-N-acetylglucosamine (O-GlcNAcylation). Further knowledge of HBP function and its response to abiotic stress may provide an alternative strategy to manipulate plant growth and tolerance to abiotic stress.

In addition to de novo biosynthesis through HBP, UDP-GlcNAc can be generated by the salvage pathway. In mammals, GlcN and GlcNAc can be retrieved from environmental resources and the degradation of glycans or glycoconjugates. These salvage nutrients can be used as dietary supplements to benefit from the treatment of disorders linked to glycosylation. GlcN can be phosphorylated to form GlcN-6-P by hexokinase and then enters the HBP to produce UDP-GlcNAc ( Figure 1 , purple line) (Kornfeld, 1967; Krug et al., 1984). In Arabidopsis, the exogenous application of GlcN to Atgfat1 mutant plants may rescue mutant phenotypes, indicating that the GlcN can be converted into GlcN-6-P, which further enters HBP to form UDP-GlcNAc (Vu et al., 2019).

GlcNAc can be phosphorylated to form GlcNAc-6-P by GlcNAc kinase (GNK) or N-acetylglucosamine kinase (NAGK) (Gindzieński et al., 1974; Allen and Walker, 1980; Hinderlich et al., 2000; Berger et al., 2002; Ryczko et al., 2016). This intermediate GlcNAc-6-P further enters the HBP to form UDP-GlcNAc ( Figure 1 , purple line). In mammals, NAGK is needed for embryonic mouse development (Dickinson et al., 2016). Deletion of NAGK increases de novo hexosamine biosynthesis; conversely, glutamine deprivation inhibits de novo HBP but triggers the NAGK-dependent salvage pathway in pancreatic ductal adenocarcinoma (PDAC) (Campbell et al., 2021), suggesting that cross-talk occurs between the salvage and de novo HBP. In higher plants, the GNK was first identified and characterized in Arabidopsis by Furo et al. (2015). Arabidopsis GNK (At1g30540) and human NAGK proteins share high structural conservation, particularly in GlcNAc and ATP binding domains. The kinase activity of AtGNK was confirmed by an enzymatic activity assay in vitro through recombinant AtGNK protein. Substrate analysis further supports that AtGNK exhibits high specificity for GlcNAc and less specificity for GalNAc. Furthermore, although the null mutant Atgnk shows no conceivable phenotype, the mutant plants reveal lower levels of UDP-GlcNAc than the wild type and are insensitive to the exogenous application of GlcNAc (Furo et al., 2015). The GlcNAc salvage pathway is also observed in the Atgna/lig mutant, which is defective in the conversion of GlcN-6-P to GlcNAc-6-P and leads to a reduction in UDP-GlcNAc levels, high-temperature sensitivity, and ectopic accumulation of lignin. Exogenous application of GlcNAc rescues the Atgna/lig mutant phenotypes and increases the UDP-GlcNAc content (Nozaki et al., 2012). Therefore, the Atgna/lig mutant fails to convert GlcN6-P to GlcNAc-6P; however, exogenous GlcNAc can be catalyzed by AtGNK to form GlcNAc-6-P, which further enters the HBP to produce UDP-GlcNAc. Similarly, wild-type plants (Col-o) produce more UDP-HexNAc (UDP-GlcNAc and UDP-GalNAc) by exogenous GlcNAc under normal and salt-stressed conditions (Chen et al., 2022). The coexistence of HBP and salvage pathways may finetune the homeostasis of UDP-GlcNAc contents in plants in response to nutrient fluctuations and environmental stimuli.

Asparagine (Asn- or N-) glycosylation is among the most common co- or post-translational modifications, which is essential for plant growth and stress responses and is conserved across eukaryotes (Banerjee et al., 2007; Bao and Howell, 2017; Nagashima et al., 2018). N-glycosylation regulates protein folding, transport, sorting, degradation, and intracellular signaling (Helenius and Aebi, 2001; Molinari, 2007; Aebi, 2013; Lannoo and Van Damme, 2015; Shin et al., 2018). Most secreted and membrane-associated proteins are N-glycosylated proteins (N-glycoproteins), and they are involved in a wide range of cellular processes, including cell wall biosynthesis (Jose-Estanyol and Puigdomenech, 2000), pollination (Hancock et al., 2005), pathogen defense (Pearce et al., 2007), and cell-to-cell communication (Taoka et al., 2007). Biosynthesis of N-glycan occurs in multiple subcellular compartments, including the cytosol, endoplasmic reticulum (ER) lumen, and Golgi apparatus (Pattison and Amtmann, 2009). Initially, N-glycan is formed as an oligosaccharide precursor on a lipid-linked carrier, dolichol pyrophosphate (PP-Dol), on the cytosolic side of the ER membrane ( Figure 2 ). Two GlcNAc molecules are first transferred to PP-Dol by GlcNAc-1-phosphotransferase (GPT) or asparagine-linked glycosylation (ALG) enzyme ALG7 and the ALG13/14. Subsequently, five mannose (Man) residues are added by mannosyltransferases, ALG1/2/11, to form Man5GlcNAc2-PP-Dol (Burda and Aebi, 1999; Strasser et al., 2021). This oligosaccharide precursor is then flipped to face the ER lumen for further modification (Pattison and Amtmann, 2009; Strasser et al., 2021).

In the ER lumen, four more Man and three Glc residues are sequentially added to form the core oligosaccharide Glc3Man9GlcNAc2-PP-Dol, which is assembled by a series of membrane-bound mannosyltransferases (ALG3/9/12) and glycosyltransferases (ALG6/8/10) (Snider et al., 1980; Helenius and Aebi, 2001; Nagashima et al., 2018; Strasser et al., 2021). N-glycosylation occurs in the ER lumen by transferring the core oligosaccharide to Asn in the Asn-X-Ser/Thr motif (X, any amino acid except Pro) of a nascent peptide, which is mediated by an oligosaccharyltransferase (OST) complex (Burda and Aebi, 1999; Pattison and Amtmann, 2009; Strasser, 2016). The N-linked Glc3Man9GlcNAc2 glycan is further processed by the sequential removal of three Glc residues by glucosidase I and II (GCSI and GCSII) (Trombetta and Parodi, 2003; Nagashima et al., 2018; Strasser et al., 2021), and a Man residue is removed by the ER-α-mannosidase I (MNS3; Liebminger et al., 2009). The correctly folded glycoproteins leave the ER and move into the Golgi apparatus for further complex and hybrid N-glycan modification (Strasser, 2016).

In the Golgi, the first N-glycan processing is carried out by α-1,2-mannosidase I (MNS1/2), which removes three Man residues from Man8GlcNAc2 to form Man5GlcNAc2, the product for the subsequent complex and hybrid N-glycan processing. The formation of complex and hybrid N-glycan is initiated by the N-ACETYLGLUCOSAMINYL TRANSFERASE I (GnTI)-mediated addition of the GlcNAc residue to the α-1,3-linked Man of the Man5GlcNAc2 to form GlcNAcMan5GlcNAc2 (von Schaewen et al., 1993; Strasser et al., 1999). Subsequently, alternative processing pathways can occur in plants (Bencúr et al., 2005). In the canonical pathway, two Man residues are cleaved from GlcNAcMan5GlcNAc by Golgi-α-mannosidase II (GMII), followed by GnTII-mediated addition of another GlcNAc residue to the α1,6-linked Man to form GlcNAc2Man3GlcNAc2. Afterward, Xyl, Fuc, and two Gal are added to the acceptor substrate GlcNAc2Man3GlcNAc2, which are catalyzed by XylT (xylosyltransferase), FUT11/12 (fucosyltransferases), and GALT1 (galactosyltransferase), respectively. Finally, FUT13 (α-(1->,4)-fucosyltransferase) transfers a Fuc residue to the α-(1->4)-linked GlcNAc to complete the Lewis A-type structure, which is a trisaccharide structure ( Figure 2 ) (Strasser, 2016; Strasser et al., 2021). The resulting products could be secreted to their destinations. Golgi-resident GnTI is the key enzyme in complex and hybrid N-glycan processing. The Arabidopsis complex glycan less 1 (cgl1) mutant, which is defective in GnTI activity, lacks complex and hybrid N-glycans and exhibits reduced N-glycosylation efficiency (von Schaewen et al., 1993; Strasser et al., 2005; Frank et al., 2008; Farid et al., 2013). However, the cgl1 mutant displays no apparent phenotype under normal growth conditions but confers salt hypersensitivity (Kang et al., 2008). In contrast to the Arabidopsis cgl1 mutant, the rice gnt1 mutant displays severe phenotypes showing arrest in postseedling development, defects in cell wall biosynthesis, and reduced cytokinin signaling (Fanata et al., 2013). The mechanisms that cause these markedly different phenotypes between Arabidopsis cgl1 and rice gnt1 remain to be illustrated in the future.

Interruption with N-glycan biosynthesis at any step by mutation of genes or treatments of pharmaceutical drugs, such as tunicamycin and DTT, will lead to incomplete N-glycans and affect N-glycosylated proteins (Pattison and Amtmann, 2009). Unfolded or misfolded proteins will accumulate in the ER and result in ER stress; eventually, the unfolded protein response (UPR) is activated to enhance the capacity for protein folding, increase the ER quality control, impair general protein translation, and maintain ER homeostasis (Bao and Howell, 2017; Yu et al., 2022). Defects in N-glycan processing may impair plant growth and stress responses or cause lethality (Lane et al., 2001; Koiwa et al., 2003; Lerouxel et al., 2005; Zhang et al., 2009; Fanata et al., 2013; Bao and Howell, 2017; Nagashima et al., 2018). Despite the significance of N-glycosylation, most studies in the past have focused on the core N-glycan formation in the ER lumen and the modification of complex N-glycans on glycoproteins in the Golgi apparatus. The effect of cytosolic oligosaccharide precursor production on plant growth and stress response is less addressed. As mentioned above, HBP generates UDP-GlcNAc to provide GlcNAc donors and initiate oligosaccharide precursor production on the cytosolic side of the ER. Defects in HBP enzymes may reduce UDP-GlcNAc levels, impair N-linked glycosylation, and alter plant growth under normal (Wang et al., 2015; Xiao et al., 2018) or abiotic stress conditions (Zhang et al., 2009; Nozaki et al., 2012; Chen et al., 2022). Moreover, a complete block of HBP normally leads to lethality (Chen et al., 2014; Vu et al., 2019; Jia et al., 2023).

It has been reported that N-glycan processing mutants alter the abiotic stress responses, such as salt stress. The staurosporine and temperature sensitive 3a (stt3a) mutant, in which a catalytic subunit of the OST complex in the ER is defective, and leaf wilting 3 (lew3), a mutant that lacks α-1,2-mannosyltransferase, induce UPR-mediated BiP gene expression and enhance salt stress sensitivity (Koiwa et al., 2003; Zhang et al., 2009; Jiao et al., 2020). However, Arabidopsis complex glycan 1 (cgl1), a mutant that lacks GnTI activity, shows a deprived complex and hybrid N-glycans and confers salt hypersensitivity (Frank et al., 2008; Kang et al., 2008). Unlike stt3a, which shows a UPR response, the cgl1 mutant fails to induce a UPR response. Thus, the UPR is likely not the major player that enhances salt hypersensitivity in the mutants with defective N-glycan processing. Furthermore, the mutation of UDP-GlcNAc transporter 1 (UGNT1) leads to deprived complex and hybrid N-glycan in the Golgi apparatus and does not increase salt hypersensitivity (Ebert et al., 2018). These data suggest that mature complex N-glycans are not the major factor leading to salt hypersensitivity. It was generally proposed that mutants defective in N-glycan processing in the ER lumen or Golgi apparatus might alter a different set of glycoprotein and/or glycolipid functions, which further integrate to alter plant growth and abiotic stress response. Compared to the Arabidopsis stt3a mutant showing short root elongation under salt stress, glcna.ut mutants, such as the RNAi knockdown mutants iU1s, display normal root elongation under salt stress (Chen et al., 2022). Although the UPR response is induced and N-linked glycosylation is impaired in iU1 mutants, these mutants exhibit salt hypersensitivity in terms of delayed seed germination and early seedling establishment, the phenotypes of which are different from those of stt3a mutant plants. The stt3a mutant, such as stt3a-2, also displays a higher stomatal density and transpiration rate in association with low endogenous ABA and auxin (IAA) levels. Thus, stt3a mutant plants are more sensitive to salt and drought stresses. These mutant phenotypes are correlated with the underglycosylation of β-glucosidase (AtBG1), catalyzing the conversion of conjugated ABA or IAA to its active form (Jiao et al., 2020). Consistently, exogenous application of ABA or IAA to stt3a-2 may partially rescue the mutant phenotypes. In contrast, the GlcNA.UT knockdown lines iU1s, reveal higher levels of ABA under salt stress conditions (Chen et al., 2022). Thus, although stt3a and iU1 affect the N-glycosylation of proteins, they could use different mechanisms in response to salt stress. It is conceivable that GlcNAc1pUTs produce UDP-GlcNAc not only for N-glycan synthesis in the ER lumen and maturation in the Golgi apparatus but also for the O-GlcNAcylation of primarily cytosolic and nuclear proteins ( Figure 2 ). Thus, in addition to N-glycan processing, HBP has a wider range of effects on plant growth and abiotic stress response through diverse GlcNAc targets or conjugates.

O-GlcNAcylation is the addition of O-linked N-acetylglucosamine (O-GlcNAc) to the serine (Ser) and threonine (Thr) residues of nucleocytoplasmic and mitochondrial proteins (Hu et al., 2009; Ma et al., 2022), which was first reported by Torres and Hart (1984). In contrast to N-linked glycosylation, which involves the attachment of complex glycans to proteins for the secretary pathway, O-GlcNAcylation involves the direct addition of a single GlcNAc residue to the Ser/Thr residues of proteins, which primarily occurs in the cytosol or nucleus ( Figure 2 ). O-GlcNAcylation is also among the most common co- or post-translational modifications and is conserved across organisms (Joshi et al., 2018; Ma et al., 2022). O-GlcNAcylated proteins are involved in most aspects of cellular functions including metabolism, transcriptional regulation, signaling, cell cycle regulation, protein trafficking, protein-protein interaction, and cell structure (Wells et al., 2001; Love and Hanover, 2005; Hart et al., 2011; Liu et al., 2022). In mammals, dysregulation of O-GlcNAcylation may be linked to chronic disorders, including the occurrence and progression of cancer (Slawson and Hart, 2011; Singh et al., 2015), diabetic complications (Peterson and Hart, 2016), neurodegeneration (Hart et al., 2011; Gong et al., 2012), and cardiovascular diseases (Wang et al., 2023), and the immune system (Golks and Guerini, 2008). Thus, manipulating O-GlcNAcylation may be a potential strategy for cancer therapy (Lu et al., 2022).

O-GlcNAcylated proteins are usually phosphorylated. As O-GlcNAcylation and phosphorylation are dynamic reactions that cycle rapidly, both post-translational modifications compete with the same Ser/Thr sites or modify nearby/or distant sites to show complex interplay and coordinate protein stability and function in response to external stimuli (Slawson and Hart, 2003; Wang et al., 2008c; Butkinaree et al., 2010; Zeidan and Hart, 2010; Hart et al., 2011; Martínez-Turiño et al., 2018; Xu et al., 2019). For instance, O-GlcNAcylation and phosphorylation coexist in the capsid protein (CP) of the plum pox virus (PPV). Although O-GlcNAcylation of PPV CP is not needed for virus viability, it increases viral infection (Pérez Jde et al., 2013; Martínez-Turiño et al., 2018). Moreover, vernalization increases the O-GlcNAc modification of nuclear TaGRP2 (a repressor in vernalization) and the phosphorylation of VER2 (an activator in vernalization); both modified proteins antagonistically regulate the expression of TaVRN1 to mediate flowering in winter wheat (Xiao et al., 2014; Xu et al., 2019).

The first public bioinformatics resource of O-GlcNAcylated proteins was established by Wang et al. (2011), in which approximately 1240 proteins are potentially O-GlcNAcylated. Later, over 1000 O-GlcNAcylated proteins were uncovered in different studies of mammalian cells (Trinidad et al., 2012; Hahne et al., 2013). Recently, with more improved techniques, over 5000 O-GlcNAcylated proteins were identified using human models (Wulff-Fuentes et al., 2021). In Arabidopsis, Xu et al. (2017) identified 262 proteins with O-GlcNAcylation. Among them, the O-GlcNAcylated and O-fucosylated protein AtACINUS is involved in ABA sensitivity through alternative splicing of HIGH LEVEL OF BETA-AMYLASE ACTIVITY 1 (HBA1) and ABA HYPERSENSITIVE 1 (ABH1), negative regulators of ABA signaling, and in flowering through transcriptional regulation of the floral repressor FLOWERING LOCUS C (FLC) (Bi et al., 2021). In addition, a total of 168 O-GlcNAcylated proteins were found in winter wheat (Xu et al., 2019); these proteins perform functions in metabolism, response to stimuli, cellular processing, signal transduction, and transcriptional regulation. Thus, the total number of identified proteins of O-GlcNAcylation is far lower in plants than in mammalian cells.

O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT) ( Figure 2 ). Phylogenetic analysis revealed that metazoans contain a single OGT, whereas vascular plants and moss have two homologs of OGTs (Olszewski et al., 2010). Considering that GlcNAc is needed for O-GlcNAcylation and UDP-GlcNAc, the donor of GlcNAc, is synthesized through HBP, HBP might perform crosstalk with O-GlcNAcylation to optimize nutrient status and O-GlcNAcylation cycling. In Drosophila, protein O-GlcNAcylation displays a circadian rhythm mediated by the HBP enzyme GFAT and the O-GlcNAcylation enzymes, OGT and O-GlcNAcase (OGA), an enzyme removing GlcNAc from O-GlcNAcylated proteins (Liu et al., 2021). The Arabidopsis knockdown mutant Atagm reduces UDP-GlcNAc production and shows a temperature-dependent growth defect that is associated with the impairment of protein O-GlcNAcylation (Jia et al., 2023). In Arabidopsis, two OGT homologs, SECRET AGENT (SEC) and SPINDLY (SPY), catalyze O-GlcNAcylation and O-linked fucosylation, respectively (Hartweck et al., 2002; Zentella et al., 2016, Zentella et al., 2017). The Arabidopsis null sec mutant only displays a subtle phenotype (Hartweck et al., 2002), but the spy mutant shows an apparent GA response, indicating that SPY acts as a negative regulator of GA signaling (Wilson and Somerville, 1995; Jacobsen et al., 1996). Moreover, the sec/spy double mutant is lethal, with defects in gamete and seed development that are similar to the knockout OGT mutants in mice and Drosophila, in which embryonic lethality occurs (Shafi et al., 2000; Gambetta et al., 2009). These data indicate that although SEC and SPY have overlapping functions involved in GA signaling, they also have distinct roles and may play a synergistic function in plant growth and development (Hartweck et al., 2002, Hartweck et al., 2006; Zentella et al., 2016, Zentella et al., 2017). Later, it was reported that the Arabidopsis sec mutant displays an early-flowering phenotype, which is associated with the inhibition of O-GlcNAcylation of ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT). The impaired activity of ATX1 reduces histone H3 lysine 4 trimethylation (H3K4me3) of the FLC gene, a negative regulator of flowering (Xing et al., 2018). The Arabidopsis DELLA protein RGA (REPRESSOR OF ga1-3), a master negative regulator of the GA response, is O-GlcNAcylated by SEC; this suppresses the interactions of RGA with other key transcription factors, such as PIFs, BZR1, and JAZ1, which are involved in light, brassinosteroid, and jasmonate signalings, respectively (Zentella et al., 2016). In addition to DELLA proteins, several important transcription factors involved in plant hormone signaling are O-GlcNAcylated, such as ARFs, TCPs, EIN2, and ABF3, which are involved in the signaling of auxin, cytokinin, ethylene, and ABA, respectively (Xu et al., 2017). Compared to mammals, numerous proteins of O-GlcNAcylation in plants remain to be uncovered, and further characterization of these modified proteins will shed light on the significance of O-GlcNAcylation biology.

UDP-GlcNAc biosynthesis through HBP is essential for the glycosylation of proteins and lipids (Ebert et al., 2018). Thus, the endogenous levels of UDP-GlcNAc levels intimately affect the glycosylation of proteins and lipids. For example, partial loss-of-function mutations in HBP-related genes normally reduce UDP-GlcNAc levels and impair N-glycosylation and/or O-GlcNAcylation of proteins (Jiang et al., 2005; Nozaki et al., 2012; Vu et al., 2019; Chen et al., 2022; Jia et al., 2023). Interestingly, these knockdown mutants largely display no apparent phenotype under normal growth conditions; however, these mutants exhibit stress-induced growth defects. This indicates that a small amount of UDP-GlcNAc is sufficient to maintain normal plant growth but more UDP-GlcNAc levels and protein glycosylation are needed for plants to adapt to deleterious environments. Most N-glycoproteins are membrane-associated and secreted proteins. Thus, changes in N-glycosylation through adverse environments or mutations of genes involved in HBP and N-glycan processing may alter glycoprotein functions in cell wall biosynthesis and integrity and membrane-associated proteins, resulting in altered sensitivities to biotic, such as bacterial blight tolerance (Wang et al., 2015), abiotic stresses, such as drought, salt, cold, and high temperature (Jiang et al., 2005; Xiao et al., 2018; Nozaki et al., 2012; Vu et al., 2019; Chen et al., 2022; Jia et al., 2023), or phytohormones, such as ABA, auxin, and JA (Zhang et al., 2009; Fanata et al., 2013; Wang et al., 2015; Jiao et al., 2020; Chen et al., 2022). Defects in N-glycoproteins might also cause the accumulation of unfolded or misfolded proteins in ER, leading to ER stress and further induction of UPR to enhance protein folding capacity and diminish ER stress (Bao and Howell, 2017; Yu et al., 2022). Therefore, ER stress or UPR can be observed in the mutations of HBP-related genes, such as GFAT, GNA, and GlcNA.UTs/or UAP/SPL29 (Xiao et al., 2018; Nozaki et al., 2012; Vu et al., 2019; Chen et al., 2022) and N-glycan processing mutants, stt3a and lew3 (Koiwa et al., 2003; Zhang et al., 2009). As UDP-GlcNAc is also essential for O-GlcNAcylation, defects in UDP-GlcNAc biosynthesis through HBP, such as AGM, or mutation of O-GlcNAcylation-related genes, such as SEC, might affect the functions of O-GlcNAcylated proteins, such as ATX1 and DELLA proteins, which further change temperature-dependent growth defects and cellular signalings, such as phytohormones ABA, GA, auxin, CK, and JA (Zentella et al., 2016; Jia et al., 2023), vernalization (Xiao et al., 2014; Xu et al., 2019), and viral infection (Pérez Jde et al., 2013; Martínez-Turiño et al., 2018). Hexosamine biosynthesis and related pathways in response to stresses are summarized in Figure 3 .

Although the HBP is considered a minor side pathway of glycolysis, it integrates the endogenous nutrient status of plants and rewires the metabolic programs to improve plant development and adaption to environmental challenges. Thus, HBP serves as a metabolic integrator or sensor to fine-tune the nutrient balance and maintain UDP-GlcNAc homeostasis. Dysfunction of HBP often causes severe phenotypes or even lethality. Research progress on HBP in plants has been much slower than that in microbes and mammals. To date, despite HBP’s studies having made a great step in plants, several aspects remain to be further explored in the future.

A better understanding of the functions of HBP, GlcNAc conjugates, and the mechanisms by which HBP responds to abiotic stress will reveal possible strategies to modify HBP in the biofortification of agriculture in the future.

Y-HC: Data curation, Writing – original draft. W-HC: Conceptualization, Funding acquisition, Writing – review & editing.