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

蝉预计其细菌透明质酸(HA)将于2025年进入市场。我们预计的5年累计利润约为520万GB(到2029年)，即项目成本的1033%投资回报率(ROI)为506,366 GB。HA广泛分布于人体和动物体内的结缔组织、上皮和神经组织。它发挥着广泛的生物学作用，被用于化妆品(例如保湿和除皱产品)、美容程序(基于HA的真皮填充物)、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)，其中医疗产品为90亿美元，化妆品为80亿美元，营养产品为30亿美元。尽管化学上很简单，但HA-生物化学是复杂的，因为它与细胞受体的相互作用因其分子量而异--这一特性为更先进的医疗产品铺平了道路。市场预计2021-2028年间的增长率为7.19%(复合年增长率)，这主要是由于人口老龄化和审美意识的增强。商业HA来自动物(鸡冠)和具有竞争力的、基于发酵的非动物产品。后者是基于细菌培养(特别是马链球菌)，这是人类的病原体。尽管有向非动物产品的强大转变，但由于蛋白质/毒素残留物的免疫原性作用，人类病原体的使用是有问题的。链球菌型HA的这一显着缺陷可能比动物源HA更大，尽管其总体蛋白质含量较低。**因此，预计微生物HA的生产将转向非致病细菌菌株**。**我们的愿景**是一种可持续的、基于生物的HA，它将刺激医学创新，降低成本，废除动物来源的HA，并将HA的用途扩大到干细胞治疗和组织工程。我们设想了一场革命，在那里，小型的数字控制的HA生物反应器由高素质的人员操作-产生很少或不产生废物，同时消耗碳并利用较少的资源密集型原料。**我们的主要目标**涉及两种非致病的工程细菌菌株的研究，它们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，并进行强有力的技术经济分析，以选择最适合扩大规模的菌株。**我们的创新**是首次尝试通过非致病性和消耗二氧化碳和/或资源密集度较低的原料的细菌菌株来生产商业HA--为新型营养食品和更低成本、更循环/可持续的HA化妆品和医疗产品铺平道路。

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.