Sustainable synthesis of Hyaluronic Acid via engineered strains of non-pathogenic bacteria - from carbon dioxide and waste feedstock to low-cost, sustainable, and waste-free Hyaluronic Acid for cosmetics, medicine, and nutraceuticals

17蝉预计其细菌透明质酸（HA）将于2025年进入市场。我们预计5年累计利润约为520万英镑（到2029年），即项目成本为506，366英镑，投资回报率（ROI）为1033%。HA广泛分布于人体和动物体内的结缔组织、上皮组织和神经组织中。它发挥着重要的生物作用，并用于化妆品（例如皮肤保湿和减少皱纹的产品）、美容程序（HA基皮肤填充剂），医疗（例如眼科手术）和有效缓解骨关节炎（通过将HA注射到关节中）。2019年HA成品的全球市场为200亿美元（Grand View Research），包括90亿美元的医疗产品，80亿美元的化妆品和30亿美元的营养产品。尽管其化学简单，HA生物化学是复杂的，因为它与细胞受体的相互作用不同，这取决于其分子量-这一特性为更先进的医疗产品铺平了道路。市场预计2021 -2028年的增长率为7.19%（复合年增长率），主要受人口老龄化和审美意识提高的推动。商业HA来源于动物（鸡冠）和竞争性的发酵非动物产品。后者是基于细菌培养（特别是_马链球菌_），这是人类病原体。尽管有向非动物产品的有力转变，但由于蛋白质/毒素残留物的免疫原性作用，使用人类病原体是有问题的。尽管链球菌-HA的总蛋白质含量较低，但该显著缺点在链球菌-HA中比在动物源HA中更大。** 因此，预计微生物HA生产将转向非致病性细菌菌株 *。我们的愿景 ** 是一个可持续的，基于生物的HA，这将刺激医疗创新，降低成本，废除动物源HA，并将HA的使用扩展到干细胞治疗和组织工程。我们设想了一场革命，小型数字控制的HA生物反应器由高素质的人员操作-产生很少或没有废物，同时消耗碳并利用资源密集度较低的原料。我们的主要目标 ** 涉及对两种工程菌株的研究，这两种菌株是非致病性的，可以消耗二氧化碳或废物原料。** 我们将专注于 ** 在连续生产中生产HA，同时进行强有力的技术经济分析，以选择最佳菌株进行放大。**我们的创新 ** 是首次尝试通过非致病性菌株生产商业HA，并且消耗二氧化碳和/或资源密集型原料较少-为新型营养品和低成本，更循环/可持续的HA化妆品和医疗产品铺平了道路。

17Cicada anticipates market entry for its bacterial Hyaluronic Acid (HA) by 2025\. Our projected cumulative 5-year profits are of the order of £5.2 million (by 2029), i.e. 1033% return on investment (ROI) on project costs of £506,366 GBP.HA is widely distributed throughout connective, epithelial and neural tissues in human and animal bodies. It plays a significant range of biological roles, and is used in cosmetics (e.g. skin-moisturising and wrinkle-reducing products), cosmetic procedures (HA-based dermal fillers), medical treatment (e.g. eye surgery) and effective relief from osteoarthritis (by injecting HA into the joints).The global market for finished HA products was $20 billion in 2019 (Grand View Research), including $9b for medical products, $8b for cosmetics and $3 billion for nutraceutical products. Despite its chemical simplicity, HA-biochemistry is complex because it interacts differently with cell receptors depending on its molecular weight -- a property which paves the way for more technologically advanced medical products. The market anticipates a growth rate of 7.19% (CAGR) between Y2021-2028, driven mainly by an aging population and increasing aesthetic consciousness.Commercial HA is sourced from animals (rooster-comb) and competing, fermentation-based, non-animal products. The latter is based on bacterial cultures (especially _Streptococcus equi_) which are human pathogens. Although there is a powerful shift towards non-animal products, the use of human pathogens is problematic due to the immunogenic effect of protein/toxin residuals. This significant drawback can be greater in streptococcal-HA than in animal-sourced HA despite its low overall protein content. **It is therefore anticipated that microbial HA-production will shift towards non-pathogenic bacterial strains**.**Our vision** is a sustainable, bio-based HA which will spur medical innovation, reduce costs, abolish animal-sourced HA, and expand use of HA into stem cell therapy and tissue engineering. We envisage a revolution where small, digitally controlled HA bioreactors are operated by highly qualified personnel -- producing little or no waste, while consuming carbon and utilising less resource-intensive feedstocks.**Our key objectives** involve research on two engineered bacterial strains which are non-pathogenic, and which can consume either carbon dioxide or waste feedstocks. **We will focus** on producing HA in continuous production, coupled with robust techno-economic analyses to select the best strain for scale-up.**Our innovation** is a first-of-a-kind attempt to produce commercial HA via bacterial strains which are non-pathogenic _and_ which consume carbon dioxide and/or less resource-intensive feedstocks -- paving the way for novel nutraceuticals and lower-cost, more circular/sustainable HA-based cosmetic and medical products.