ÔØ ÅÒÙ×Ö ÔØ Taurine: A critical nutrient for future fish feeds Guillaume P. Salze, D. Allen Davis PII: S0044-8486(14)00629-2 DOI: doi: 10.1016/j.aquaculture.2014.12.006 Reference: AQUA 631469 To appear in: Aquaculture Received date: 22 August 2014 Revised date: 3 December 2014 Accepted date: 4 December 2014 Please cite this article as: Salze, Guillaume P., Davis, D. Allen, Taurine: A critical nutrient for future fish feeds, Aquaculture (2014), doi: 10.1016/j.aquaculture.2014.12.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Taurine: A critical nutrient for future fish feeds Guillaume P. Salze and D. Allen Davis School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, 203 Swingle Hall, Auburn, AL 36849-5419, USA Abstract Taurine is a sulfonic acid found in high concentrations in animal tissues. In recent years, a number of studies have demonstrated the essentiality of dietary taurine for many commercially relevant species, especially marine teleosts. Consequently, the removal of taurine-rich dietary ingredients such as fishmeal may create a deficiency, of which symptoms include reduced growth and survival, increased susceptibility to diseases, and impaired larval development. These symptoms emphasize the systemic role of taurine in the animal’s physiology and provide few clues as to the underlying mechanisms of taurine function. In fact, a myriad of roles have been attributed to taurine in mammals, ranging from bile salt conjugation to membrane stabilization, osmoregulation, anti-oxidation, immunomodulation, calcium-signaling, and neuroprotection. This review describes the current knowledge of taurine physiology and metabolism in fish and requirement levels in relevant species, and highlights possible parallels with mammalian taurine metabolism. In addition, the effects of ingredient processing and feed ACCEPTED MANUSCRIPT manufacturing on taurine bioavailability are discussed. Finally, regulatory aspects are brought to the forefront: although the supplementation of taurine will be necessary to further reduce the use of ingredients such as fishmeal, taurine is not currently approved by the FDA in the USA for fish feeds. Obtaining approval in the United States to utilize taurine in fish feeds can improve the environmental and economic sustainability of fish feeds nation-wide. Keywords: Fishmeal replacement; taurine; regulations; requirement; biosynthetic pathway 1 ACCEPTED MANUSCRIPT 1 Introduction Taurine (2-aminoethanesulfonic acid, CAS 107-35-7) is an organic acid which was first described from ox bile (Tiedemann and Gmelin, 1827). Taurine is a simple molecule, containing an acidic sulfonate group, a basic amino group, and two carbons in between. It is therefore an amino acid, albeit a β-amino acid: the amino group is bound to the carbon adjacent to the one holding the acidic group (i.e., the second carbon, β). This is in contrast to α-amino acids where the amino group is bound to the same carbon holding the acidic group (i.e., first carbon, α). There is also no tRNA encoding for taurine and its sulfonate group replaces the carboxyl group necessary for the formation of a peptide bond. Consequently, taurine cannot be part of translated peptide chains, although there are naturally occurring, taurine-containing peptides (Bittner et al., 2005; Lähdesmäki, 1987). The amine group allows for quantitation by using the same methodology used for other amino acids (typically High Performance Liquid Chromatography, HPCL) and analysis results are often reported together. Taurine exists naturally in animals including mammals, birds, fish, and aquatic invertebrates such as oysters and mussels. Although plants contain less than 1% of the taurine levels found in animals, the most taurine-rich plants are algae, followed by fungi and other terrestrial plants (Kataoka and Ohnishi, 1986). High taurine levels naturally occur in seafood and meat, and many vertebrates can synthesize taurine. On the other hand, certain animals, includingACCEPTED species containing high MANUSCRIPTlevels of taurine, cannot metabolically synthesize taurine and require dietary sources for physiological processes. Taurine is the most abundant free amino acid in animal tissues, accounting for 25% of the free amino acid pool in liver, 50% in kidney, 53% in muscle and 19% in brain (Brosnan and Brosnan, 2006). In mammals, taurine is involved in a particularly wide variety of functions including constituent of bile, osmoregulation, cell membrane stabilization, anti- oxidation, and calcium signaling required in vertebrates for normal cardiac, skeletal muscle, nervous, and retinal function (Bouckenooghe et al., 2006; Huxtable, 1992). 2 ACCEPTED MANUSCRIPT Approximately 5,000-6,000 tons of taurine (synthetic and purified from natural sources) were produced in the world in 1993, and were divided at 50% for pet food manufacturing, and 50% for pharmaceutical applications (Tully, 2000). An updated global production is difficult to estimate and would require a full market analysis. Three Chinese manufacturers each advertise a production of 15- 96,000 metric tons per year (source: Alibaba.com), although these numbers cannot be verified. However, there is no doubt that today’s production is considerably higher than it was in 1993. Currently, global taurine production is destined to three main uses: cat food, infant formulas and the beverage industry for “energy” drinks. According to manufacturers, taurine products are crystalline powders more than 98.5% pure and conform to standards of the United States, Japan, and Europe. To our knowledge, all products are based on the 98.5% purity level, hence there is no food or feed grade taurine. Taurine can be produced either by extraction and purification from taurine-rich sources (Takahashi, 1986) or by chemical synthesis. The majority of taurine is produced by chemical synthesis because extraction is less efficient, more costly, and initial materials (e.g., bovine or ovine bile) are not available in sufficient amounts to meet the global market demand (Chen, 2014). To our knowledge, taurine can be chemically synthesized by five chemical processes: 1) amination of the isethionic acid resulting from the reaction of ethylene oxide and sodium bisulfite, 2) combination of aziridine and sulfurous acid, 3) reaction of methionine, vitamin E,ACCEPTED and cysteine, 4) formation MANUSCRIPTof salt from monoethanolamine and sulfuric acid, followed by reduction with sodium sulfite or sodium carbonate or 5) sulfonation of ethylene chloride by sodium bisulfite prior to reaction with anhydrous ammonia or ammonium cabonate. The fourth method (monoethanolamine-based) results in 98.5% pure taurine, thus matching the purity level of commercially available taurine. This suggests that this method may be the most used for taurine production, although this is difficult to ascertain without a global survey of the industry. 3 ACCEPTED MANUSCRIPT Novel methods also include the genetic modification of prokaryote or eukaryote cells to increase taurine biosynthesis (Turano et al., 2012). However taurine produced by such method is not currently available commercially. 2 Regulation and policies Regulations of taurine use in people, pet, or animal feeds varies widely depending on the country under consideration. In the European Union the Observed Safe Level (OSL) is estimated to be 100 mg taurine per kg body weight per day for people, and synthetic taurine is considered efficacious in cats, dogs, and carnivorous fish diets (EFSA, 2012). In China taurine is authorized for fish feed in all species, and listed as a nutrition enhancer for children (GB-2760-2011 Food Safety National Standards for the Usage of Food Additives) and maximum permissible values are given for some human food items such as jelly, milk, and energy drinks (GB14880-2012 Food Safety National Standards for the Usage of Nutrition Enrichment). In Japan taurine is listed among “substances designated as having no potential to cause damage to human health” (Japanese Ministry of Health, Labor and Welfare). It is also designated as a feed additive which can be used in fish and other livestock, although quantities are not regulated (Japanese Ministry of Agriculture,ACCEPTED Forestry and Fisheries, MANUSCRIPT Food and Agricultural Materials Inspection Center). Finally, in Australia, feed supplements whose purpose is to ingredients supplying a nutrient required by the livestock do not require registration (Australian Pesticide and Veterinary Medicines Authority, APVMA). As such, the use of the use of taurine is allowed without registration, for as long as the dose is limited to meeting the nutritional requirement. If included beyond this point, it is considered a veterinary chemical and thus requires registration to the APVMA. In the USA however, taurine is not listed by the Food and Drug Administration (FDA) as a food substance generally recognized as safe for human consumption and is considered a drug or additive (Code for Federal Regulations: 21 CFR 104.2, 4 ACCEPTED MANUSCRIPT 21 CFR 184, and 21 CFR 186). Taurine use is permitted as a nutritional supplement in chicken