SuCCEED: Sustainable Commodity Chemicals through Enzyme Engineering & Design

商品化学品支撑着现代日常生活的各个方面，并在全球范围内大量生产。它们支撑着塑料/聚合物、染料/颜料、化妆品/洗涤剂等的生产，通常来自有限的地质资源。鉴于需要走向更可持续和循环的经济，迫切需要可行的商品化学品生物生产途径。这类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散装规模运营。这给商业化部署带来了重大障碍，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。除了经济和技术方面的挑战外，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，发酵过程中相对缓慢的产物积累经常导致下游副反应。尽管如此，据报道，有多种途径可以获得各种感兴趣的商品化学品，但由于这些原因，它们的生产率很低。相比之下，发酵可以产生高水平的生物相容性前体，如乙醇/乳酸等，经常用于酿造/乳制品行业。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，我们建议现有的和新的生物途径的商品化学品将受益于类似的两步方法。在第一步，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，我们将使用酶转化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由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。作为原理验证，我们最近将该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，类似的战略可以成功地应用于生产更广泛的商品化学品，包括醛、二烯、二羧酸等。为此，我们汇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，为使用发酵后酶转化可扩展生产多种商品化学品提供原理证明，以支持可行的生物精炼厂的创建。

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.