Genetic Regulation of Phytic Acid Biosynthesis in Rice: Pathways and Breeding Approaches for Low-Phytate Varieties

doi:10.1016/j.rsci.2025.10.003

Abstract

Abstract:

Phytic acid (PA), or myo-inositol 1,2,3,4,5,6-hexakisphosphate, is the main storage form of phosphorus (P) in seeds, accounting for 65% to 85% of their total P content. The negative charge of PA attracts metal cations, forming insoluble salts called phytates. These phytates, contain six negatively charged ions, can bind divalent cations such as Fe²⁺, Zn²⁺, Mg²⁺, and Ca²⁺, preventing their absorption in monogastric animals. To overcome P deficiency in non-ruminants, phytase is usually given as a supplement, which then results in excess P excretion, leading to environmental problems such as eutrophication. Improved fertilizer management, food processing techniques, and the development of low-PA crops through plant breeding are envisioned as effective ways to improve P-utilization and lessen the environmental impact while minimizing the effect of PA. A better understanding of the molecular and physiological basis of PA biosynthesis, grain PA distribution, the effects of genetic and environmental factors on PA accumulation, and methods to increase micronutrient bioavailability by lowering the effects of PA is essential for developing low-PA crops.

Key words: phytic acid, mineral, mitigation, metabolism, myo-inositol, lpa mutant

Lishali Desingu, R. L. Visakh, R. P. Sah, Uday Chand Jha, R. V. Manju, Swapna Alex, Radha Beena. Genetic Regulation of Phytic Acid Biosynthesis in Rice: Pathways and Breeding Approaches for Low-Phytate Varieties[J]. Rice Science, 2025, 32(6): 797-812.

Figures/Tables 5

References 123

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Gene/Enzyme	Species	Function in phytic acid regulation	Reference
IPK1 (Inositol pentakisphosphate 2-kinase)	Arabidopsis thaliana, Phaseolus vulgaris, Glycine max, Triticum aestivum, Oryza sativa	Regulates the last step of phytic acid synthesis, converting InsP5 to InsP6	Fileppi et al (2010); Vincent et al (2015); Kuo et al (2018); Ibrahim et al (2024); Wang et al (2024)
IPK2 (Inositol polyphosphate kinase 2)	A. thaliana, P. vulgaris, O. sativa, G. max	Facilitates the conversion of lower inositol phosphates into higher forms in lipid-dependent phytic acid production	Xu et al (2005); Suzuki et al (2007); Fileppi et al (2010); Marathe et al (2018)
INO1 (myo-Inositol-3-phosphate synthase 1)	G. max, O. sativa	Encodes myo-inositol-3-phosphate synthase	Hegeman et al (2001); Perera et al (2019)
MIPS (myo-Inositol-1-phosphate synthase)	Hordeum vulgare, Zea mays, P. vulgaris, Arachis hypogea, Cicer arietinum, Cajanus cajan, G. max, Lablab purpureus, Medicago truncatula, Pisum sativum, Trifolium pratense, Vigna unguiculata	Involved in transformation of myo- inositol-3-phosphate from glucose-6-phosphate	Larson and Raboy (1999); Fileppi et al (2010); Jacob et al (2024)
MIK (myo-Inositol kinase)	Z. mays, P. vulgaris, O. sativa	Converts myo-inositol to inositol monophosphate, which initiates phytic acid biosynthesis pathway	Shi et al (2005); Fileppi et al (2010); Zhao et al (2013)
MRP (ABC transporter)	O. sativa, A. thaliana, T. aestivum, Z. mays	Accountable for lpa1 mutation, affecting the regulation of phytic acid pathway	Garcia et al (2004), Bhati et al (2015), Yang et al (2024)
LPA1 (Low phytic acid 1), LPA2 (Low phytic acid 2), LPA3 (Low phytic acid 3)	T. aestivum, O. sativa, Z. mays	Mutation leads to reduced phytic acid content in seeds	Venegas et al (2018), Kishor et al (2019), Yathish et al (2023), K R et al (2025)
ITPK (Inositol 1,3,4-trisphosphate 5/6-kinase)	G. max, P. vulgaris, A. thaliana, O. sativa	Encodes inositol tetrakisphosphate kinase, which catalyzes the phosphorylation of inositol pentakisphosphate (IP5) to inositol hexakisphosphate (IP6)	Stiles et al (2008); Fileppi et al (2010); Laha et al (2019); Karmakar et al (2020)

Gene/Enzyme	Species	Function in phytic acid regulation	Reference
IPK1 (Inositol pentakisphosphate 2-kinase)	Arabidopsis thaliana, Phaseolus vulgaris, Glycine max, Triticum aestivum, Oryza sativa	Regulates the last step of phytic acid synthesis, converting InsP5 to InsP6	Fileppi et al (2010); Vincent et al (2015); Kuo et al (2018); Ibrahim et al (2024); Wang et al (2024)
IPK2 (Inositol polyphosphate kinase 2)	A. thaliana, P. vulgaris, O. sativa, G. max	Facilitates the conversion of lower inositol phosphates into higher forms in lipid-dependent phytic acid production	Xu et al (2005); Suzuki et al (2007); Fileppi et al (2010); Marathe et al (2018)
INO1 (myo-Inositol-3-phosphate synthase 1)	G. max, O. sativa	Encodes myo-inositol-3-phosphate synthase	Hegeman et al (2001); Perera et al (2019)
MIPS (myo-Inositol-1-phosphate synthase)	Hordeum vulgare, Zea mays, P. vulgaris, Arachis hypogea, Cicer arietinum, Cajanus cajan, G. max, Lablab purpureus, Medicago truncatula, Pisum sativum, Trifolium pratense, Vigna unguiculata	Involved in transformation of myo- inositol-3-phosphate from glucose-6-phosphate	Larson and Raboy (1999); Fileppi et al (2010); Jacob et al (2024)
MIK (myo-Inositol kinase)	Z. mays, P. vulgaris, O. sativa	Converts myo-inositol to inositol monophosphate, which initiates phytic acid biosynthesis pathway	Shi et al (2005); Fileppi et al (2010); Zhao et al (2013)
MRP (ABC transporter)	O. sativa, A. thaliana, T. aestivum, Z. mays	Accountable for lpa1 mutation, affecting the regulation of phytic acid pathway	Garcia et al (2004), Bhati et al (2015), Yang et al (2024)
LPA1 (Low phytic acid 1), LPA2 (Low phytic acid 2), LPA3 (Low phytic acid 3)	T. aestivum, O. sativa, Z. mays	Mutation leads to reduced phytic acid content in seeds	Venegas et al (2018), Kishor et al (2019), Yathish et al (2023), K R et al (2025)
ITPK (Inositol 1,3,4-trisphosphate 5/6-kinase)	G. max, P. vulgaris, A. thaliana, O. sativa	Encodes inositol tetrakisphosphate kinase, which catalyzes the phosphorylation of inositol pentakisphosphate (IP5) to inositol hexakisphosphate (IP6)	Stiles et al (2008); Fileppi et al (2010); Laha et al (2019); Karmakar et al (2020)

Plant species	Targeted gene	Approach used	PA reduced (%)	Promoter employed	Yield penality	Reference
Arabidopsis thaliana	ITPK4, MRP5	EMS Mu insertion	‒	‒	‒	Ren et al, 2024
Triticum durum	TdMRP3	TILLING	85	‒	17.7% reduction of spikelet number per panicle and 34.5% reduction of grain number per spikelet	Frittelli et al, 2023
Glycine max	GmIPK1	CRISPR/Cas9	< 25	GmU6-10 promoter to drive sgRNAs and AtRPS5A promoter for Cas9 expression	‒	Song et al, 2022
Triticum aestivum	TaIPK1	CRISPR/Cas9	70	TaU6 promoter to control sgRNAs and OsUbi promoter for Cas9 gene	‒	Ibrahim et al, 2022
Zea mays	ZmMRP4	EMS	< 36	‒	‒	Abhijith et al, 2020
Brassica napus	BnITPK1, BnITPK4	CRISPR/Cas9	< 35	AtU6-26 promoter to drive expression of sgRNAs and Ubi4-2 promoter to drive Cas9 gene	No statistically significant reduction	Sashidhar et al, 2020
Oryza sativa	OsITPK6	CRISPR/Cas9	< 32	‒	Decreased grain yield and seed viability	Jiang et al, 2019
Glycine max	GmMIPS1	Antisense and RNAi	38‒41	Seed-specific vicilin promoter	Shorter plant height and root length, and less number of pods per plant	Kumar et al, 2019
Glycine max	GmIPK2	RNAi	45	Seed-specific vicilin promoter	No statistically significant reduction	Punjabi et al, 2018
Triticum aestivum	TaABCC13	RNAi	22‒34	pMCG161 RNAi vector	Grain filling and seed-setting rate were significantly affected	Bhati et al, 2016
Oryza sativa	OsMIK	Hairpin RNA and artificial microRNA-mediated gene silencing	14‒50	Ole18 to drive seed-specific expression	‒	Li et al, 2014
Oryza sativa	OsIPK1	RNAi	50-69	Ole18	‒	Ali et al, 2013a

Plant species	Targeted gene	Approach used	PA reduced (%)	Promoter employed	Yield penality	Reference
Arabidopsis thaliana	ITPK4, MRP5	EMS Mu insertion	‒	‒	‒	Ren et al, 2024
Triticum durum	TdMRP3	TILLING	85	‒	17.7% reduction of spikelet number per panicle and 34.5% reduction of grain number per spikelet	Frittelli et al, 2023
Glycine max	GmIPK1	CRISPR/Cas9	< 25	GmU6-10 promoter to drive sgRNAs and AtRPS5A promoter for Cas9 expression	‒	Song et al, 2022
Triticum aestivum	TaIPK1	CRISPR/Cas9	70	TaU6 promoter to control sgRNAs and OsUbi promoter for Cas9 gene	‒	Ibrahim et al, 2022
Zea mays	ZmMRP4	EMS	< 36	‒	‒	Abhijith et al, 2020
Brassica napus	BnITPK1, BnITPK4	CRISPR/Cas9	< 35	AtU6-26 promoter to drive expression of sgRNAs and Ubi4-2 promoter to drive Cas9 gene	No statistically significant reduction	Sashidhar et al, 2020
Oryza sativa	OsITPK6	CRISPR/Cas9	< 32	‒	Decreased grain yield and seed viability	Jiang et al, 2019
Glycine max	GmMIPS1	Antisense and RNAi	38‒41	Seed-specific vicilin promoter	Shorter plant height and root length, and less number of pods per plant	Kumar et al, 2019
Glycine max	GmIPK2	RNAi	45	Seed-specific vicilin promoter	No statistically significant reduction	Punjabi et al, 2018
Triticum aestivum	TaABCC13	RNAi	22‒34	pMCG161 RNAi vector	Grain filling and seed-setting rate were significantly affected	Bhati et al, 2016
Oryza sativa	OsMIK	Hairpin RNA and artificial microRNA-mediated gene silencing	14‒50	Ole18 to drive seed-specific expression	‒	Li et al, 2014
Oryza sativa	OsIPK1	RNAi	50-69	Ole18	‒	Ali et al, 2013a