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(12) Patent Application Publication (10) Pub. No.: US 2012/0222148A1 Turano Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2012/0222148A1 Turano Et Al US 20120222148A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0222148A1 Turano et al. (43) Pub. Date: Aug. 30, 2012 (54) METHODS FOR THE BIOSYNTHESIS OF AOIH 5/10 (2006.01) TAURINE OR HYPOTAURINE IN CELLS AOIH 5/08 (2006.01) A636/00 (2006.01) (75) Inventors: Frank J. Turano, Baltimore, MD CI2N 5/82 (2006.01) (US); Kathleen A. Turano, (52) U.S. Cl. ......... 800/260; 424/725; 426/615; 426/635; Baltimore, MD (US); Peters. 435/468; 435/411; 435/412: 435/415; 435/417: Carlson, Baltimore, MD (US); 435/419: 800/278; 800/290; 800/298; 800/301; Alan M. Kinnersley, Baltimore, 800/302:800/305; 800/307; 800/308; 800/309; MD (US) 800/310: 800/312:800/313; 800/314; 800/315; (73) Assignee: PLANT SENSORY SYSTEMS Sooo... LLC, Baltimore, MD (US) •800/320.1; - s 800/320.2:of 800/320.3s (21) Appl. No.: 131505,415 (57) ABSTRACT (22) PCT Filed: Oct. 29, 2010 The present invention describes an approach to increase tau rine or hypotaurine production in prokaryotes or eukaryotes. (86). PCT No.: PCT/US2O1 O/O54664 More particularly, the invention relates to genetic transforma tion of organisms with genes that encode proteins that cata S371 (c)(1), lyze the conversion of cysteine to taurine, methionine to tau (2), (4) Date: May 1, 2012 rine, cysteamine to taurine, or alanine to taurine. The invention describes methods for the use of polynucleotides Related U.S. Application Data that encode functional cysteine dioxygenase (CDO), cysteine (60) 2,Provisional 2009, provisional application application No. 61/257.240, No. 61/263,548, filed on Nov.filed orE. glutamate decarboxyE. s aseyine ( ), cysteamine E. dioxygenase ase (SAD) (ADO), taurine-pyruvate aminotransferase (TPAT), TPAT on Nov. 23, 2009. and Sulfoacetaldehyde acetyltransferase (SA), taurine dioxy O O genase (TDO) or the small (ssTDeHase) and large subunits of Publication Classification taurine dehydrogenase (1sTDeHase) polypeptides in plants to (51) Int. Cl. increase taurine, hypotaurine or taurine precursor production. AOIH IM02 (2006.01) The preferred embodiment of the invention is in plants but A2.3L. I./22 (2006.01) other organisms may be used. Increased taurine production in A23K L/00 (2006.01) plants will enhance plant growth and development, yield, or AOIH 5/06 (2006.01) tolerance to biotic and/or abiotic stresses and could be used as CI2N 5/10 (2006.01) nutraceutical, pharmaceutical, or therapeutic compounds or AOIH 5/00 (2006.01) as a Supplement in animal feed. Patent Application Publication Aug. 30, 2012 US 2012/0222148A1 FIGURE I Cysteine se CDO 3-sulfinoalanine CL SAD Cysteamine Cysteate O GAD ADO SUCCinate SAD Hypotaurine Sulfite Or HTDeHase 2-oxoglutarate GAD TDO Pyruvate Taurine TPAT TDeHase Alanine Sulfo- Ammonium acetaldehyde Orthophosphate SA Acetyl Sulfite phosphate US 2012/0222148 A1 Aug. 30, 2012 METHODS FOR THE BIOSYNTHESIS OF 0005 Taurine is an Essential Compound for Animals TAURINE OR HYPOTAURINE IN CELLS 0006 Taurine is essential for human neonatal develop ment (2) and plays an important role in brain development (3. CROSS REFERENCE TO RELATED 4). Taurine is involved in the modulation of intracellular calcium homeostasis (5, 6) and may balance glutamate activ APPLICATION(S) ity, protecting neurons against glutamate excitotoxicity (7,8). 0001. This application claims the benefit of U.S. Patent Taurine is also an osmoregulator (9). Taurine is essential for Application No. 61/257.240 filed Nov. 2, 2009 and U.S. heart function (10), protects the integrity of hepatic tissue Patent Application No. 61/263,548 filed Nov. 23, 2009, the (11), and plays a role in photoprotection (12). disclosures of which are incorporated herein in their entirety 0007 Taurine as a Pharmaceutical or Therapeutic by reference. 0008 Taurine is used as a pharmaceutical and therapeutic. Taurine has been used in the treatment of cardiovascular diseases (13, 14), elevated blood pressure (15), seizure disor FIELD OF THE INVENTION ders (16), hepatic disorders (17), and alcoholism (18) and 0002 The present invention is in the field of recombinant may be useful in the treatment of diabetes (19), Alzheimer's production of taurine. disease (20), and ocular disorders (21). Taurine has been shown to prevent obesity (22) and control cholesterol (23. 24). Taurine acts as an antioxidant and protects against tox BACKGROUND OF THE INVENTION icity of various substances (25-27). Taurine has been shown to prevent oxidative stress induced by exercise (28), and is used 0003 Taurine as a Plant Growth Stimulator in energy drinks to improve performance (29). Taurine can 0004 Exogenous application of taurine has been reported also be used in topical applications to treat dermatological to increase crop harvest, yield, and biomass (1). Applications conditions (30). of taurine by foliar spray, Soil and roots application, and seed 0009 Taurine as a Dietary Supplement immersion increase crop production and seedling growth (1). 0010 Taurine is biosynthesized in most animals and can Exogenous applications of taurine have also been shown to be found in meat and seafood. Those who do not eat these increase photosynthetic capacity of isolated plant cells (pro foods regularly (e.g., vegetarians) or do not produce Sufficient toplasts and chloroplasts) (1). Increased taurine production in levels of taurine, e.g., cats (31), must acquire it through plants can enhance plant growth and development, yield, or dietary supplement. Trout that are fed all-plant protein diets tolerance to biotic and/or abiotic stresses. Increased yield, must acquire dietary taurine for normal growth (32). growth, or biomass may be a result of increased nitrogen flow, (0011 Metabolic Pathways that Synthesize Taurine sensing, uptake, storage, transport or nitrogen use efficiency. 0012. With few exceptions (33, 34), taurine is found in Increased yield, growth or biomass may also be a result of plants only in low levels (35), and the metabolic pathway for increased carbon metabolism due to increased photosynthesis taurine and hypotaurine has not yet been identified in plants. or increased carbohydrate metabolism by increased Sucrose Several metabolic pathways that synthesize taurine and hypo production and/or transport or increase biosynthesis or mobi taurine have been identified in animals and bacteria (FIG. 1). lization of starch, or oil. Increased yield, growth or biomass In animals, cysteine and oxygen are converted into 3-sulfi may also be associated with increased phosphorus uptake, noalanine by cysteine dioxygenase (CDO). 3-sulfinoalanine transport or utilization. Increased yield, growth or biomass is converted into hypotaurine by Sulfinoalanine decarboxy may also be associated with increased Sulfur or Sulfate lase (SAD) or glutamate decarboxylase (GAD). Hypotaurine uptake, transport or utilization. Increased yield, growth or is converted into taurine either by the activity of hypotaurine biomass may also be associated with increased water uptake, dehydrogenase (HTDeHase) or by a spontaneous conversion. transport, utilization or water-use-efficiency. Increased yield, Cysteamine (2-aminoethanethiol) and oxygen are converted growth or biomass may also be due to changes in the cell cycle into hypotaurine by cysteamine dioxygenase (ADO), and modifications that improve growth rates and may increase hypotaurine is converted into taurine. Alternatively cysteine early vigor and accelerate maturation leading to improved and Sulfite are converted into cysteate and hydrogen sulfide by yield. Increased yield, growth or biomass may also be due to cysteine lyase (cysteine Sulfite lyase or cysteine hydrogen changes in the production of hormones or signaling mol sulfide-lyase). Cysteate is converted into taurine by SAD or ecules that regulate and improve plant growth and develop GAD. In bacteria, the compound 2-sulfoacetaldehyde is syn ment leading to improvements in yield and biotic or abiotic thesized from acetyl phosphate and sulfite by sulfoacetalde stress tolerance. Increases in carbon, nitrogen, phosphorus, or hyde acetyltransferase (SA). Alanine and 2-sulfoacetalde Sulfate flow, sensing, uptake, storage, transport or efficiency hyde are converted into taurine and pyruvate by taurine may improve seed quality for starch, oil or protein content. pyruvate aminotransferase (TPAT). In addition, Increased yield, growth or biomass may also be a result of Sulfoacetaldehyde and ammonia (or ammonium) are con increased tolerance to abiotic stress such as changes in verted into taurine and water in the presence of ferrocyto osmotic conditions, oxidative damage, drought, salt, cold, chrome C by taurine dehydrogenase. Sulfite, aminoacetalde freezing, heat, UV light or light intensity. Increased yield, hyde, carbon dioxide and Succinate are converted into taurine, growth or biomass may also be a result of increased tolerance 2-oxoglutarate and oxygen by taurine dioxygenase (TDO). to biotic stress such as challenges, infection or insult from pests, pathogens, bacteria, microbes, viruses, Viroids, micro SUMMARY OF THE INVENTION organisms, invertebrates, insects, nematodes, or vertebrate. 0013 The invention provides methods and compositions Increased yield, growth or biomass may be a result of for taurine or taurine precursor production in organisms. increased tolerance to abiotic stresses such as changes in More particularly, the invention encompasses the use of poly osmotic conditions or light intensity, oxidative damage, nucleotides that encode in plants functional (1) cysteine drought, salt, cold, freezing, heat, or UV radiation. dioxygenase (CDO),
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