SBIR Phase I: Production of an affordable synthetic colostrum replacer in edible green algae

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力将是开发一种替代抗生素在农业和伴侣动物中的使用的方法。最近有证据表明，给牲畜喂食抗生素的做法与感染人类的耐抗生素细菌菌株的出现有关。出于这个原因，FDA最近推出了一项自愿计划，逐步停止在动物身上使用抗生素。然而，为了保护动物健康和促进体重增加而使用抗生素在畜牧业中很普遍，因此需要一种可行且无害的替代品。这项拟议中的技术将允许牲畜种植者通过喂养可食用的绿藻来保护他们的动物，并促进体重增加，这些绿藻经过改造可以产生初乳蛋白质。初乳蛋白被认为具有与抗生素相同的保护作用，而且没有产生耐抗生素细菌的负面副作用。在绿藻中生产这些初乳蛋白允许高效的生物制造，这将满足为牲畜生产者提供具有成本效益的初乳来源所需的规模。用于动物健康和增重的抗生素每年的销售额达到数十亿美元，随着该行业逐渐放弃使用抗生素，这种新方法有可能在该市场占据相当大的份额。这个SBIR项目提议开发能产生初乳蛋白的绿藻基因工程菌株——莱茵衣原体瘤。初乳蛋白通常被摄入消化道，在那里它们表现出抗微生物的特性。莱茵梭菌已被证明具有必要的细胞机制来产生广泛的复杂蛋白质，包括单克隆抗体、激素等。目标是在莱茵梭菌中产生几种关键的初乳蛋白质，这些蛋白质将作为抗生素的替代品喂给牲畜，并包括在伴侣动物的饮食中。拟议的研究将证明，藻类中产生的初乳蛋白质具有生物活性，并将以与天然蛋白质相同的方式发挥作用。此外，该研究将生产一种培养基，用于种植可食用的藻类，这种藻类对动物消费是安全的，并促进感兴趣的初乳蛋白的表达。最后，研究将证明藻类表达的初乳蛋白对动物健康和促进生长有有益的作用。总之，这项研究将有助于证明在牲畜饲料中使用藻类表达的初乳蛋白替代抗生素使用以及在宠物食品中促进宠物健康的可行性。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will be to develop an alternative to the use of antibiotics in agricultural and companion animals. It has recently been demonstrated that the practice of feeding antibiotics to livestock is correlated with the emergence of antibiotic resistant strains of bacteria that infect humans. For this reason, the FDA has recently introduced a voluntary plan to phase out the use of antibiotics in animals. However, antibiotic use to protect animal health and to promote weight gain is widespread in the livestock industry, and a viable and non-harmful alternative is needed. The proposed technology will allow livestock growers to protect their animals and promote weight gain by feeding edible green algae that have been engineered to produce colostrum proteins. Colostrum proteins are thought to have the same protective effects as antibiotics without the negative side effect of producing antibiotic resistant bacteria. Production of these colostrum proteins in green algae allows for efficient bio-manufacturing, which will meet the scale required to supply livestock producers with a cost effective source of colostrum. Sales of antibiotics for animal health and weight gain are in the billions of dollars each year, and this new approach has the potential to garner a significant share of that market as the industry shifts away from the use of antibiotics. This SBIR project proposes to develop genetically engineered strains of green algae, Chlamydomomas reinhardtii, that produce colostrum proteins. Colostrum proteins are normally ingested into the digestive tract where they exhibit anti-microbial properties. C. reinhardtii has been shown to have the necessary cellular machinery to produce a wide range of complex proteins including monoclonal antibodies, hormones, and others. The goal is to produce several key colostrum proteins in C. reinhardtii that will be fed to livestock as a replacement for antibiotics, and be included in companion animal diets. The proposed research will demonstrate that colostrum proteins produced in algae are bioactive, and will function in the same manner as their natural counterparts. Additionally, the research will produce a media in which to grow edible algae that is safe for animal consumption and promotes the expression of the colostrum protein of interest. Finally, the research will demonstrate that algal expressed colostrum proteins have a beneficial effect on animal health and growth promotion. Together, this research will help demonstrate the feasibility of using algal-expressed colostrum proteins as a replacement for antibiotic use in livestock feeds and promotion of pet health in pet food.