Bioproduction of a high-value synthetic ketone ester and its precursors for a UK-based value and supply chain

高价值合成酮酯及其前体的生物生产，用于英国的价值和供应链

• 批准号: BB/V001396/1
• 负责人: John Heap
• 金额: $ 29.29万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV001396%2F1
• 关键词: Bioproduction; value; synthetic; ketone; ester

Biological technologies are important in the production of many types of products, and will become increasingly important in future, for several reasons:(1) Much conventional manufacturing relies on energy and/or chemicals generated from fossil carbon resources, but there is an urgent need to transition to environmentally and economically sustainable circular economies in order to decrease greenhouse gas emissions, limit climate change and limit environmental degradation. Biological technologies can provide sustainable alternatives.(2) Biological technologies are, or could be, superior to conventional non-biological methods of producing some types of products, because they provide important advantages in the efficiency, costs, and control over some types of chemical reactions.(3) Biologically active chemicals are important in medicine, nutrition and agriculture, all of which are actively growing and developing areas in which many new products can be expected. Biological technologies often have advantages in production of these types of chemicals.(4) The transition to sustainable circular economies and development of the above types of products represent huge economic opportunities for advanced, high-tech economies like the UK, the US and EU to develop, exploit and export the technologies that will be required.This project is focused on a new product called ketone ester and two key chemical precursors used in its production, called (R)-3-hydroxybutyrate (R3HB) and (R)-1,3-butanediol (R13BD). Ketone ester is a 'nutraceutical'. Nutraceuticals are a class of products consumed as nutritional supplements, but which provide additional benefits beyond regular food or nutrients, of the kind more commonly associated with pharmaceuticals, hence the term nutraceutical.Development and commercialisation of ketone ester is the focus of University of Oxford spin-out company TdeltaS. TdeltaS has performed many studies showing that ketone ester is safe to consume as a drink, and once inside the body is quickly broken down into natural 'ketone bodies' with beneficial effects. Ketone bodies are exceptional sources of energy, and are especially good at providing energy to the brain and blood. Ketone bodies are naturally found in the human body, but are only usually made during starvation or during special diets which can cause health problems. Consumption of ketone ester provides a rapid, safe and convenient way to obtain the benefits of ketone bodies, and studies have found benefits in enhancing athletic performance, in defence, and the potential to treat various diseases. Crucially, ketone ester has regulatory approval and has already reached a high-value market as a consumer nutraceutical in the US. Great demand for ketone ester, particularly from athletes, has rapidly outstripped supply.Developing a reliable UK supply of R3HB and R13BD as chemical precursors for ketone ester would improve the scale of production and commercial success of ketone ester, allowing the market to grow to reflect the great demand. R3HB and R13BD also have many other uses as chemicals in other industries, with established markets. The chemical structures of R3HB and R13BD mean they can be very effectively produced by biotechnological means.This project's industrial partner, CHAIN Biotechnology, has previously generated engineered microbial strains which produce R3HB and R13BD, but only in mixtures with other products, which does not suit the current aim.The overall aim of this project is to apply the combined expertise, experience and capacity of the academic applicants and industrial partner CHAIN Biotechnology to develop new strains of microorganisms which produce R3HB and/or R13BD well enough that they could be used to manufacture these chemicals. The project will also demonstrate production of the ketone ester itself in engineered cells, which could lead to a simpler biomanufacturing process for ketone ester in future.

生物技术在许多类型产品的生产中非常重要，并且在未来将变得越来越重要，原因如下：（1）许多传统制造业依赖于化石碳资源产生的能源和/或化学品，但迫切需要向环境和经济可持续的循环经济过渡，以减少温室气体排放，限制气候变化和限制环境退化。生物技术可以提供可持续的替代办法。(2)生物技术是，或可能是，上级生产某些类型的产品的传统非生物方法，因为它们提供了重要的优势，在效率，成本，和控制某些类型的化学反应。(3)生物活性化学品在医药、营养和农业中很重要，所有这些领域都在积极发展和开发，预计会有许多新产品。生物技术在生产这类化学品方面往往具有优势。(4)向可持续循环经济的过渡和上述类型产品的发展为英国、美国和欧盟等先进的高科技经济体提供了巨大的经济机会，可以开发、利用和出口所需的技术。该项目的重点是一种名为酮酯的新产品及其生产中使用的两种关键化学前体，称为（R）-3-羟基丁酸酯（R3 HB）和（R）-1，3-丁二醇（R13 BD）。酮酯是一种“营养品”。营养保健品是一类作为营养补充剂消费的产品，但它提供了常规食物或营养素之外的额外益处，更常见的是与药物相关的那种，因此术语营养保健品。酮酯的开发和商业化是牛津大学分拆公司TdeltaS的重点。TdeltaS进行了许多研究表明，酮酯作为饮料是安全的，一旦进入体内，就会迅速分解为具有有益效果的天然“酮体”。酮体是能量的特殊来源，特别擅长为大脑和血液提供能量。酮体在人体中自然存在，但通常只在饥饿或特殊饮食期间产生，这可能会导致健康问题。酮酯的消耗提供了一种快速，安全和方便的方式来获得酮体的益处，并且研究发现了在提高运动成绩，防御和治疗各种疾病的潜力方面的益处。至关重要的是，酮酯已获得监管机构批准，并已作为美国消费者营养药进入高价值市场。酮酯的巨大需求，特别是运动员的需求，已经迅速超过了供应。开发一个可靠的英国供应的R3 HB和R13 BD作为酮酯的化学前体将提高酮酯的生产规模和商业成功，使市场增长，以反映巨大的需求。R3 HB和R13 BD在其他工业中也有许多其他用途，作为化学品，具有成熟的市场。R3 HB和R13 BD的化学结构意味着它们可以通过生物技术手段非常有效地生产。该项目的工业合作伙伴CHAIN Biotechnology先前已经产生了生产R3 HB和R13 BD的工程微生物菌株，但仅与其他产品混合，这不符合当前的目标。该项目的总体目标是应用组合的专业知识，学术申请人和工业合作伙伴链生物技术的经验和能力，以开发新的微生物菌株，产生R3 HB和/或R13 BD足够好，他们可以用来制造这些化学品。该项目还将展示在工程细胞中生产酮酯本身，这可能会导致未来酮酯的生物制造过程更简单。