SuCCEED: Sustainable Commodity Chemicals through Enzyme Engineering & Design

SuCCEED：通过酶工程实现可持续商品化学品

• 批准号: BB/Y003276/1
• 负责人: David Leys
• 金额: $ 389.11万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY003276%2F1
• 关键词: SuCCEED; Sustainable; Commodity; Chemicals; through

Commodity chemicals underpin various aspect of modern everyday life, and are mass produced on a global scale. They underpin the production of plastics/polymers, dyes/pigments, cosmetics/detergents etc, and are normally derived from finite geological sources. In view of the need to move towards a more sustainable and circular economy, viable routes for the bioproduction of commodity chemicals are urgently required. One of the key challenges for such routes is that they must operate at relatively low profit margins and at appropriate bulk scale. This presents a significant hurdle to commercial deployment, but, given the scale of commodity chemical production, viable biomanufacturing routes would offer substantial impact upon the global efforts to reduce CO2 emissions. In addition to the challenges posed at economic and technical levels, the very nature of most commodity chemicals all too often renders them incompatible with direct production by microorganisms. This is due to the inherent reactivity and associated toxicity of these compounds. Furthermore, the relatively slow accumulation of the product during fermentation all too frequently leads to downstream side reactions. Nevertheless, various routes to a wide range of commodity chemicals of interest have been reported, but suffer from low productivity for these reasons. By contrast, fermentation can yield high levels of biocompatible precursors such as ethanol/lactic acid etc as frequently used in brewing/diary industry. These compounds in turn can be converted to a limited range of commodity chemicals through downstream processes. By analogy, we propose that both existing and novel bioroutes to commodity chemicals would benefit from a similar two-step approach. In the first step, we seek to achieve accumulation of suitable biocompatible precursors from 2G/3G derived biomass. In the second step, we will use enzymatic conversion to yield the desired commodity chemical product. Crucially, separation of microbial growth from chemical production is afforded by such a two-step process, bypassing the issue of toxicity/side-reactions during fermentation. As a proof-of-principle, we recently applied this strategy to bio-styrene production, achieving a 5-fold increase on styrene production levels compared to previous methods. In collaboration with Shell, we seek to further enhance the new styrene bioproduction process and demonstrate production at scales appropriate for further industrial development. Furthermore, we seek to demonstrate that similar strategies can be successfully applied to the production of a wider range of commodity chemicals, including aldehydes, dienes, dicarboxylic acids etc. To this end, we have brought together an interdisciplinary team of biochemists, protein engineers, synthetic biologists, chemists and chemical engineers to provide proof-of-principle for scalable production of multiple commodity chemicals using post-fermentative enzymatic conversion to support creation of viable biorefineries.

日用化学品支撑着现代日常生活的各个方面，并在全球范围内大规模生产。它们是塑料/聚合物、染料/颜料、化妆品/洗涤剂等生产的基础，通常来自有限的地质来源。鉴于有必要逐步实现更可持续的循环经济，迫切需要找到可行的生物生产商品化学品的途径。这些航线面临的主要挑战之一是，它们必须以相对较低的利润率和适当的批量规模运营。这对商业部署构成了重大障碍，但鉴于商品化学品生产的规模，可行的生物制造路线将对全球减少二氧化碳排放的努力产生重大影响。除了在经济和技术层面上构成的挑战外，大多数商品化学品的性质往往使其与微生物直接生产不相容。这是由于这些化合物的固有反应性和相关毒性。此外，在发酵期间产物的相对缓慢的积累太频繁地导致下游副反应。尽管如此，已经报道了多种获得感兴趣的商品化学品的途径，但由于这些原因，生产率低。相比之下，发酵可以产生高水平的生物相容性前体，如在酿造/乳制品工业中经常使用的乙醇/乳酸等。这些化合物又可以通过下游工艺转化为有限范围的商品化学品。通过类比，我们提出，现有的和新的生物路线的商品化学品将受益于类似的两步走的方法。在第一步中，我们寻求从2G/3G衍生的生物质中积累合适的生物相容性前体。在第二步中，我们将使用酶转化来产生所需的商品化学产品。至关重要的是，微生物生长与化学生产的分离是通过这样的两步过程提供的，绕过了发酵过程中的毒性/副反应问题。作为原理证明，我们最近将这种策略应用于生物苯乙烯生产，与以前的方法相比，苯乙烯生产水平提高了5倍。通过与壳牌公司的合作，我们寻求进一步加强新的苯乙烯生物生产工艺，并展示适合进一步工业发展的规模生产。此外，我们试图证明，类似的策略可以成功地应用于更广泛的商品化学品的生产，包括醛，二烯，二羧酸等，为此，我们汇集了生物化学家，蛋白质工程师，合成生物学家，化学家和化学工程师，为使用后处理技术的多种商品化学品的可规模化生产提供原理证明，发酵酶转化以支持可行的生物精炼厂的创建。