SuCCEED: Sustainable Commodity Chemicals through Enzyme Engineering & Design

商品化学品是现代日常生活的各个方面的基础，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。鉴于需要走向更可持续和更循环的经济，迫切需要生物生产商品化学品的可行途径。这类航线的关键挑战之一是，它们必须以相对较低的利润率和适当的大宗规模运营。这对商业部署来说是一个重大障碍，但考虑到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。除了经济和技术层面的挑战外，大多数商品化学品的性质往往使它们与微生物直接生产不相容。这是由于这些化合物固有的反应性和相关的毒性。此外，发酵过程中产物的积累相对较慢，经常导致下游副反应。尽管如此，已经报道了获得各种感兴趣的商品化学品的各种途径，但由于这些原因，生产率较低。相比之下，发酵可以产生高水平的生物相容前体，如酿造/乳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，现有的和新的到商品化学品的生物路线都将受益于类似的两步法。在第一步中，我们寻求从2G/3G来源的生物质中积累合适的生物相容前体。在第二步中，我们将使用酶转化来生产所需的商品化工产品。最重要的是，这种两步法可实现微生物生长与化学生产的分离，绕过发酵过程中的毒性/副反应问题。作为一项原则证明，我们最近将这一策略应用于生物苯乙烯的生产，实现了与以前方法相比，苯乙烯产量水平提高了5倍。通过与壳牌的合作，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、二元酸等。为此，我们聚集了一个由生物化学家、蛋白质工程师、合成生物学家、化学家和化学工程师组成的跨学科团队，为利用发酵后酶促转化实现多种商品化学品的可规模化生产提供原理证明，以支持创建可行的生物精炼厂。

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.