Plant Synthetic Metabolic Engineering for Enhancing Crop Nutritional Quality

Nutrient deficiencies in crops are a serious threat to human health, especially for populations in poor areas. To overcome this problem, the development of crops with nutrient-enhanced traits is imperative. Biofortification of crops to improve nutritional quality helps combat nutrient deficiencies by increasing the levels of specific nutrient components. Compared with agronomic practices and conventional plant breeding, plant metabolic engineering and synthetic biology strategies are more effective and accurate in synthesizing specific micronutrients, phytonutrients, and/or bioactive components in crops. In this review, we discuss recent progress in the field of plant synthetic metabolic engineering, specifically in terms of research strategies of multigene stacking tools and engineering complex metabolic pathways, with a focus on improving traits related to micronutrients, phytonutrients, and bioactive components. Advances and innovations in plant synthetic metabolic engineering would facilitate the development of nutrient-enriched crops to meet the nutritional needs of humans.

[1]  N. Han,et al.  Overexpression of HvHGGT Enhances Tocotrienol Levels and Antioxidant Activity in Barley. , 2017, Journal of agricultural and food chemistry.

[2]  S. McGuire,et al.  FAO, IFAD, and WFP. The State of Food Insecurity in the World 2015: Meeting the 2015 International Hunger Targets: Taking Stock of Uneven Progress. Rome: FAO, 2015. , 2015, Advances in nutrition.

[3]  M. Ahn,et al.  A single amino acid change at position 96 (Arg to His) of the sweetpotato Orange protein leads to carotenoid overaccumulation , 2019, Plant Cell Reports.

[4]  A. Prasad Trace elements and iron in human metabolism , 1978 .

[5]  Chunyi Zhang,et al.  Synthesis of Seed-Specific Bidirectional Promoters for Metabolic Engineering of Anthocyanin-Rich Maize , 2018, Plant & cell physiology.

[6]  D. G. Gibson,et al.  Enzymatic assembly of DNA molecules up to several hundred kilobases , 2009, Nature Methods.

[7]  Jürgen Breitenbach,et al.  Combinatorial genetic transformation generates a library of metabolic phenotypes for the carotenoid pathway in maize , 2008, Proceedings of the National Academy of Sciences.

[8]  J. Napier,et al.  A nutritionally-enhanced oil from transgenic Camelina sativa effectively replaces fish oil as a source of eicosapentaenoic acid for fish , 2015, Scientific Reports.

[9]  J. Napier,et al.  Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop , 2013, The Plant journal : for cell and molecular biology.

[10]  Wei Chen,et al.  Canola engineered with a microalgal polyketide synthase-like system produces oil enriched in docosahexaenoic acid , 2016, Nature Biotechnology.

[11]  W. Gruissem,et al.  Single genetic locus improvement of iron, zinc and β-carotene content in rice grains , 2017, Scientific Reports.

[12]  Xianchang Yu,et al.  Ascorbic acid contents in transgenic potato plants overexpressing two dehydroascorbate reductase genes , 2011, Molecular Biology Reports.

[13]  D. Van Der Straeten,et al.  Toward Eradication of B-Vitamin Deficiencies: Considerations for Crop Biofortification , 2018, Front. Plant Sci..

[14]  R. E. Burch,et al.  Trace elements in human nutrition. , 1979, The Medical clinics of North America.

[15]  P. Broun,et al.  Genetic engineering of plant lipids. , 1999, Annual review of nutrition.

[16]  R. Hall,et al.  Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors , 2008, Nature Biotechnology.

[17]  X. Fang,et al.  Engineering purple rice for human health , 2018, Science China Life Sciences.

[18]  K. Glassman,et al.  Elevated vitamin E content improves all-trans β-carotene accumulation and stability in biofortified sorghum , 2016, Proceedings of the National Academy of Sciences.

[19]  Raúl García-Granados,et al.  Metabolic Engineering and Synthetic Biology: Synergies, Future, and Challenges , 2019, Front. Bioeng. Biotechnol..

[20]  Blake L. Joyce,et al.  Ketocarotenoid Production in Soybean Seeds through Metabolic Engineering , 2015, PloS one.

[21]  L. Xiong,et al.  Enhancement of vitamin B(6) levels in seeds through metabolic engineering. , 2009, Plant biotechnology journal.

[22]  T. Tzfira,et al.  pSAT RNA Interference Vectors: A Modular Series for Multiple Gene Down-Regulation in Plants1[OA] , 2007, Plant Physiology.

[23]  A. Allan,et al.  Enhancing ascorbate in fruits and tubers through over-expression of the L-galactose pathway gene GDP-L-galactose phosphorylase. , 2012, Plant biotechnology journal.

[24]  Thomas F. Knight,et al.  Idempotent Vector Design for Standard Assembly of Biobricks , 2003 .

[25]  R. Srivastava,et al.  Crop biofortification for iron (Fe), zinc (Zn) and vitamin A with transgenic approaches , 2019, Heliyon.

[26]  A. Mattoo,et al.  Genetic engineering to enhance crop-based phytonutrients (nutraceuticals) to alleviate diet-related diseases. , 2010, Advances in experimental medicine and biology.

[27]  T. Thannhauser,et al.  Arabidopsis OR proteins are the major posttranscriptional regulators of phytoene synthase in controlling carotenoid biosynthesis , 2015, Proceedings of the National Academy of Sciences.

[28]  R. Visser,et al.  Folate Biofortification of Potato by Tuber-Specific Expression of Four Folate Biosynthesis Genes. , 2018, Molecular plant.

[29]  Ning Tang,et al.  SlMYB75, an MYB-type transcription factor, promotes anthocyanin accumulation and enhances volatile aroma production in tomato fruits , 2019, Horticulture Research.

[30]  G. Sandmann,et al.  Metabolic engineering of tomato for high-yield production of astaxanthin. , 2013, Metabolic engineering.

[31]  H. Yasuda,et al.  High accumulation of bioactive peptide in transgenic rice seeds by expression of introduced multiple genes. , 2006, Plant biotechnology journal.

[32]  T. Tzfira,et al.  Zinc Finger Nuclease and Homing Endonuclease-Mediated Assembly of Multigene Plant Transformation Vectors1[OA] , 2011, Plant Physiology.

[33]  D. Van Der Straeten,et al.  From in planta Function to Vitamin-Rich Food Crops: The ACE of Biofortification , 2018, Front. Plant Sci..

[34]  P. Christou,et al.  Constitutive Expression of Soybean Ferritin cDNA Intransgenic Wheat and Rice Results in Increased Iron Levels in Vegetative Tissues but not in Seeds , 2000, Transgenic Research.

[35]  J. Forment,et al.  GoldenBraid 2.0: A Comprehensive DNA Assembly Framework for Plant Synthetic Biology1[C][W][OA] , 2013, Plant Physiology.

[36]  R. Thilmony,et al.  A versatile and robust Agrobacterium‐based gene stacking system generates high‐quality transgenic Arabidopsis plants , 2018, The Plant journal : for cell and molecular biology.

[37]  A. Fernie,et al.  Multi-level engineering facilitates the production of phenylpropanoid compounds in tomato , 2015, Nature Communications.

[38]  Judith Hodge Hidden Hunger Approaches to Tackling Micronutrient Deficiencies , 2016 .

[39]  P. Lucca,et al.  Genetic engineering approaches to improve the bioavailability and the level of iron in rice grains , 2001, Theoretical and Applied Genetics.

[40]  C. Ruxton,et al.  The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. , 2004, Journal of human nutrition and dietetics : the official journal of the British Dietetic Association.

[41]  Golden Mh Trace elements in human nutrition. , 1982 .

[42]  W. Broekaert,et al.  A set of modular plant transformation vectors allowing flexible insertion of up to six expression units , 2002, Plant Molecular Biology.

[43]  N. Rigby,et al.  A Transgenic Camelina sativa Seed Oil Effectively Replaces Fish Oil as a Dietary Source of Eicosapentaenoic Acid in Mice123 , 2016, The Journal of nutrition.

[44]  F. Shah,et al.  Bioengineered Plants Can Be a Useful Source of Omega-3 Fatty Acids , 2017, BioMed research international.

[45]  Hai-Meng Zhou,et al.  A Gateway-based platform for multigene plant transformation , 2006, Plant Molecular Biology.

[46]  Li Li,et al.  The Cauliflower Or Gene Encodes a DnaJ Cysteine-Rich Domain-Containing Protein That Mediates High Levels of β-Carotene Accumulation[W] , 2006, The Plant Cell Online.

[47]  R. Bock Strategies for metabolic pathway engineering with multiple transgenes , 2013, Plant Molecular Biology.

[48]  J. K. Kim,et al.  Stepwise pathway engineering to the biosynthesis of zeaxanthin, astaxanthin and capsanthin in rice endosperm. , 2019, Metabolic engineering.

[49]  Zengyi Shao,et al.  DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways , 2008, Nucleic acids research.

[50]  G. An,et al.  Transgenic rice lines expressing maize C1 and R-S regulatory genes produce various flavonoids in the endosperm. , 2006, Plant biotechnology journal.

[51]  A. Bovy,et al.  Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols , 2001, Nature Biotechnology.

[52]  Xavier Gellynck,et al.  GM biofortified crops: potential effects on targeting the micronutrient intake gap in human populations. , 2017, Current opinion in biotechnology.

[53]  A. Hanson,et al.  Synthetic biology meets plant metabolism. , 2018, Plant science : an international journal of experimental plant biology.

[54]  D. Van Der Straeten,et al.  Engineering complex metabolic pathways in plants. , 2014, Annual review of plant biology.

[55]  Cathie Martin,et al.  Next-Generation Plant Metabolic Engineering, Inspired by an Ancient Chinese Irrigation System. , 2018, Molecular plant.

[56]  V. Lipka,et al.  COLORFUL-Circuit: A Platform for Rapid Multigene Assembly, Delivery, and Expression in Plants , 2016, Front. Plant Sci..

[57]  Jia Chen,et al.  MISSA Is a Highly Efficient in Vivo DNA Assembly Method for Plant Multiple-Gene Transformation1[C][W] , 2010, Plant Physiology.

[58]  Qinlong Zhu,et al.  Development of "Purple Endosperm Rice" by Engineering Anthocyanin Biosynthesis in the Endosperm with a High-Efficiency Transgene Stacking System. , 2017, Molecular plant.

[59]  S. Abdullah,et al.  Advances in Genetic Improvement for Tocotrienol Production: A Review. , 2017, Journal of nutritional science and vitaminology.

[60]  Xinxiang Peng,et al.  Engineering a New Chloroplastic Photorespiratory Bypass to Increase Photosynthetic Efficiency and Productivity in Rice. , 2019, Molecular plant.

[61]  Peter D. Nichols,et al.  Metabolic Engineering Camelina sativa with Fish Oil-Like Levels of DHA , 2014, PloS one.

[62]  Carola Engler,et al.  A One Pot, One Step, Precision Cloning Method with High Throughput Capability , 2008, PloS one.

[63]  T. Vanhercke,et al.  From plant metabolic engineering to plant synthetic biology: The evolution of the design/build/test/learn cycle. , 2018, Plant science : an international journal of experimental plant biology.

[64]  Jürgen Breitenbach,et al.  Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways , 2009, Proceedings of the National Academy of Sciences.

[65]  J. Gregory,et al.  Folate biofortification in tomatoes by engineering the pteridine branch of folate synthesis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Cathie Martin,et al.  Engineering anthocyanin biosynthesis in plants. , 2014, Current opinion in plant biology.

[67]  Qinlong Zhu,et al.  From Golden Rice to aSTARice: Bioengineering Astaxanthin Biosynthesis in Rice Endosperm. , 2018, Molecular plant.

[68]  E. Schijlen,et al.  High-Flavonol Tomatoes Resulting from the Heterologous Expression of the Maize Transcription Factor Genes LC and C1 Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.004218. , 2002, The Plant Cell Online.

[69]  Qing Liu,et al.  Metabolic Engineering Plant Seeds with Fish Oil-Like Levels of DHA , 2012, PloS one.

[70]  J. P. Peña-Rosas,et al.  Staple crops biofortified with increased vitamins and minerals: considerations for a public health strategy , 2017, Annals of the New York Academy of Sciences.

[71]  Barbara A Halkier,et al.  USER cloning and USER fusion: the ideal cloning techniques for small and big laboratories. , 2010, Methods in molecular biology.

[72]  Takayuki Tohge,et al.  Rice endosperm iron biofortification by targeted and synergistic action of nicotianamine synthase and ferritin. , 2009, Plant biotechnology journal.

[73]  Chunyi Zhang,et al.  Engineering of ‘Purple Embryo Maize’ with a multigene expression system derived from a bidirectional promoter and self‐cleaving 2A peptides , 2018, Plant biotechnology journal.

[74]  Christian Kappel,et al.  Recent advances in the transcriptional regulation of the flavonoid biosynthetic pathway. , 2011, Journal of experimental botany.

[75]  S. Elledge,et al.  Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC , 2007, Nature Methods.

[76]  H. Shou,et al.  Nicotianamine, a Novel Enhancer of Rice Iron Bioavailability to Humans , 2010, PloS one.

[77]  J. Napier,et al.  Transgenic plants as a sustainable, terrestrial source of fish oils , 2015, European journal of lipid science and technology : EJLST.

[78]  R. Dixon,et al.  Metabolic engineering of anthocyanins and condensed tannins in plants. , 2013, Current opinion in biotechnology.

[79]  A. Xiong,et al.  Enhancing carotenoid biosynthesis in rice endosperm by metabolic engineering , 2019, Plant biotechnology journal.

[80]  H. Steur,et al.  Metabolic engineering of micronutrients in crop plants , 2017, Annals of the New York Academy of Sciences.

[81]  J.-H. Sheen,et al.  A potent Cas9-derived gene activator for plant and mammalian cells , 2017, Nature Plants.

[82]  T. Tzfira,et al.  Delivery of Multiple Transgenes to Plant Cells1[C] , 2007, Plant Physiology.

[83]  Jakob Skoet The State of Food Insecurity in the World , 2006 .

[84]  M. Aluru,et al.  Genetic modification of low phytic acid 1-1 maize to enhance iron content and bioavailability. , 2011, Journal of agricultural and food chemistry.

[85]  Wusheng Liu,et al.  Plant synthetic biology. , 2015, Trends in plant science.

[86]  J. Dinneny,et al.  A robust family of Golden Gate Agrobacterium vectors for plant synthetic biology , 2013, Front. Plant Sci..

[87]  Takeshi Omasa,et al.  Synthetic metabolic engineering-a novel, simple technology for designing a chimeric metabolic pathway , 2012, Microbial Cell Factories.

[88]  Herbert M. Sauro,et al.  In-Fusion BioBrick assembly and re-engineering , 2010, Nucleic acids research.

[89]  E. Hinchliffe,et al.  Improving the nutritional value of Golden Rice through increased pro-vitamin A content , 2005, Nature Biotechnology.

[90]  Wusheng Liu,et al.  Advanced genetic tools for plant biotechnology , 2013, Nature Reviews Genetics.

[91]  C. Ruxton,et al.  The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. , 2007, Journal of human nutrition and dietetics : the official journal of the British Dietetic Association.

[92]  Aman Kumar,et al.  Biofortified Crops Generated by Breeding, Agronomy, and Transgenic Approaches Are Improving Lives of Millions of People around the World , 2018, Front. Nutr..

[93]  S. Toki,et al.  Iron fortification of rice seed by the soybean ferritin gene , 1999, Nature Biotechnology.

[94]  Christian R. Boehm,et al.  Recent Advances and Current Challenges in Synthetic Biology of the Plastid Genetic System and Metabolism[OPEN] , 2018, Plant Physiology.

[95]  E. Grotewold,et al.  Metabolic engineering to enhance the value of plants as green factories. , 2015, Metabolic engineering.

[96]  P. Christou,et al.  Metabolic engineering of ketocarotenoid biosynthesis in higher plants. , 2009, Archives of biochemistry and biophysics.

[97]  M. Zeller,et al.  Availability, production, and consumption of crops biofortified by plant breeding: current evidence and future potential , 2017, Annals of the New York Academy of Sciences.

[98]  J. Sugimoto,et al.  The Global Hidden Hunger Indices and Maps: An Advocacy Tool for Action , 2013, PloS one.

[99]  P. Christou,et al.  Bottlenecks in carotenoid biosynthesis and accumulation in rice endosperm are influenced by the precursor-product balance. , 2016, Plant biotechnology journal.

[100]  Yuan Zhang,et al.  Phenolic Compounds and Bioactivities of Pigmented Rice , 2013, Critical reviews in food science and nutrition.

[101]  J Craig Venter,et al.  One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome , 2008, Proceedings of the National Academy of Sciences.

[102]  D. Ow Recombinase-mediated gene stacking as a transformation operating system. , 2011, Journal of integrative plant biology.

[103]  J. Napier,et al.  Metabolic engineering of the omega-3 long chain polyunsaturated fatty acid biosynthetic pathway into transgenic plants. , 2012, Journal of experimental botany.

[104]  Luke A. Gilbert,et al.  Engineering Complex Synthetic Transcriptional Programs with CRISPR RNA Scaffolds , 2015, Cell.

[105]  Z. Fei,et al.  Ectopic expression of ORANGE promotes carotenoid accumulation and fruit development in tomato , 2018, Plant biotechnology journal.

[106]  Tsutomu Ishimaru,et al.  Transgenic rice seed synthesizing diverse flavonoids at high levels: a new platform for flavonoid production with associated health benefits. , 2013, Plant biotechnology journal.

[107]  Benjamin P. Bowen,et al.  A robust gene-stacking method utilizing yeast assembly for plant synthetic biology , 2016, Nature Communications.

[108]  Yaoguang Liu,et al.  Efficient linking and transfer of multiple genes by a multigene assembly and transformation vector system , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[109]  J. Napier,et al.  Reconstitution of EPA and DHA biosynthesis in Arabidopsis: Iterative metabolic engineering for the synthesis of n−3 LC-PUFAs in transgenic plants , 2013, Metabolic engineering.

[110]  X. Chen,et al.  Enrichment of provitamin A content in wheat (Triticum aestivum L.) by introduction of the bacterial carotenoid biosynthetic genes CrtB and CrtI , 2014, Journal of experimental botany.

[111]  Xiao Qiu,et al.  Stepwise engineering to produce high yields of very long-chain polyunsaturated fatty acids in plants , 2005, Nature Biotechnology.

[112]  R. Twyman,et al.  Promoter diversity in multigene transformation , 2010, Plant Molecular Biology.

[113]  Yao-wu Yuan,et al.  Transcriptional Regulation of Carotenoid Biosynthesis in Plants: So Many Regulators, So Little Consensus , 2019, Front. Plant Sci..

[114]  S. Storozhenko,et al.  Improving folate (vitamin B9) stability in biofortified rice through metabolic engineering , 2015, Nature Biotechnology.

[115]  D. Salt,et al.  Iron-Induced Turnover of the Arabidopsis IRON-REGULATED TRANSPORTER1 Metal Transporter Requires Lysine Residues1[W][OA] , 2008, Plant Physiology.

[116]  Jenny C Mortimer,et al.  Plant synthetic biology could drive a revolution in biofuels and medicine , 2018, Experimental biology and medicine.

[117]  Gynheung An,et al.  Iron fortification of rice seeds through activation of the nicotianamine synthase gene , 2009, Proceedings of the National Academy of Sciences.

[118]  W. Gruissem,et al.  Increased bioavailable vitamin B6 in field-grown transgenic cassava for dietary sufficiency , 2015, Nature Biotechnology.

[119]  P. Beyer,et al.  Engineering the provitamin A (beta-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm. , 2000, Science.

[120]  A. Vainstein,et al.  pSAT vectors: a modular series of plasmids for autofluorescent protein tagging and expression of multiple genes in plants , 2005, Plant Molecular Biology.

[121]  S. Storozhenko,et al.  Folate fortification of rice by metabolic engineering , 2007, Nature Biotechnology.

[122]  H. Brinch-Pedersen,et al.  Wheat ferritins: Improving the iron content of the wheat grain , 2012 .

[123]  Jens Nielsen,et al.  Synergies between synthetic biology and metabolic engineering , 2011, Nature Biotechnology.

[124]  M. Vidal,et al.  GATEWAY recombinational cloning: application to the cloning of large numbers of open reading frames or ORFeomes. , 2000, Methods in enzymology.