Thinking big: towards ideal strains and processes for large-scale aerobic biofuels production.
Thinking big: towards ideal strains and processes for large-scale aerobic biofuels production.
复制标题
大思考：迈向大型有氧生物燃料生产的理想菌株和过程。
DOI：
10.1111/1751-7915.12471
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发表时间：
2017-01
影响因子：
5.7
通讯作者：
Beckham GT
中科院分区：
文献类型：
--
作者：
McMillan JD;Beckham GT
全球对人为气候变化、能源安全和独立性以及持续开采化石燃料的环境后果的关切，正在推动公共和私营部门的重大兴趣和资金，以加快开发和部署生产可再生燃料以及生物基化学品和材料的工艺，以达到与目前化石燃料生产相称的规模。在过去的二十年中，由主要来自甘蔗和淀粉的第一代己糖生产乙醇的厌氧微生物在全球范围内已经达到了显著的市场份额，发酵生物反应器的规模通常超过百万升规模。最近，出现了工业规模的木质纤维素乙醇工厂，其使用类似于第一代生物精炼厂的基因工程微生物和生物反应器规模从戊糖和己糖生产乙醇。随着木质纤维素燃料乙醇工业的兴起，学术界和政府科学界资助的研究在很大程度上将其研究和开发重点转移到生产生物燃料，这些燃料可以直接替代化石柴油，汽油和喷气燃料。这一研究重点反映了基础设施兼容性的局限性和与乙醇作为燃料混合料相关的（真实的或感知的）担忧，以及通过代谢工程和合成生物学的进步而出现的微生物遗传修饰新能力的日益增长的前景。对于主要通过微生物产生的生物燃料，大多数提出的目标直接燃料或燃料前体是或将通过碳代谢中的“深层”途径产生的，例如脂肪酸、类异戊二烯或聚酮化合物合成途径（Peralta-Yahya等人，2012年）。关于最佳代谢工程、系统生物学和合成生物学策略，已经发表了无数的观点、评论和原始研究报告，用于使用这些途径生产直接生物燃料或燃料前体。毫无疑问，这种重定向中央碳代谢的总体战略对于开发能够生产适用于多种运输市场的一系列生物燃料以及生产各种商品和精细化学品的菌株具有很大的前景。虽然可以通过上述代谢途径生产各种各样的直接生物燃料和生物基产品，但这些途径迄今为止仅已知在有氧条件下具有高生产力。这是因为这些合成途径产生烃或近烃产物（如脂肪酸和长链烷烃）是代谢性的“上坡”合成代谢途径，需要ATP和NAD（P）H形式的能量来实现高生产率，即与用于生产乙醇的代谢性的“下坡”分解代谢途径相反。通过厌氧发酵生产丁醇（或丁醇或短链羧酸），其是净ATP阳性的、氧化还原平衡的，并且可以厌氧进行。使用需要有氧呼吸以产生驱动它们所需的能量的代谢途径，虽然对于生产高价值的精细化学品、治疗剂、氨基酸、抗生素以及甚至一些更高价值的商品化学品是合理的，但对大容量、低成本燃料的经济生产构成了严重挑战。这主要是由于向浸没式培养物供应氧气（O2）所需的额外资本和操作成本，其次是由于扩大好氧工艺与厌氧工艺的规模经济降低。例如，有氧运动的成本较高...
Global concerns about anthropogenic climate change, energy security and independence, and environmental consequences of continued fossil fuel exploitation are driving significant public and private sector interest and financing to hasten development and deployment of processes to produce renewable fuels, as well as bio-based chemicals and materials, towards scales commensurate with current fossil fuel-based production. Over the past two decades, anaerobic microbial production of ethanol from first-generation hexose sugars derived primarily from sugarcane and starch has reached significant market share worldwide, with fermentation bioreactor sizes often exceeding the million litre scale. More recently, industrial-scale lignocellulosic ethanol plants are emerging that produce ethanol from pentose and hexose sugars using genetically engineered microbes and bioreactor scales similar to first-generation biorefineries. Concomitant with the genesis of a lignocellulosic fuel ethanol industry, publicly funded research by the academic and governmental scientific community has largely shifted its research and development emphasis to producing biofuels that can be drop-in replacements for fossil-based diesel, gasoline and jet fuels. This research pivot reflects both limitations in infrastructure compatibility and associated (real or perceived) concerns with ethanol as a fuel blendstock, as well as growing promise of new capabilities in microbial genetic modification emerging through advances in metabolic engineering and synthetic biology. For biofuels produced primarily via microbes, most proposed target drop-in fuels or fuel precursors are or will be produced via pathways ‘deep’in carbon metabolism, such as fatty acid, isoprenoid or polyketide synthesis pathways (Peralta-Yahya et al., 2012). Myriad perspectives, reviews and original research reports have been published regarding optimal metabolic engineering, systems biology, and synthetic biology strategies for producing drop-in biofuels or fuel precursors using these pathways. Undoubtedly, this overarching strategy to redirect central carbon metabolism exhibits great promise for developing strains capable of producing a range of biofuels suitable for multiple transportation markets and for producing a wide variety of commodity and fine chemicals. While a wide range of drop-in biofuels and bio-based products can be produced via the aforementioned metabolic pathways, these pathways are as yet only known to be highly productive under aerobic conditions. This is because these synthesis pathways to produce hydrocarbon or near-hydrocarbon products (eg fatty acids and long-chain alkanes) are thermodynamically ‘uphill’anabolic metabolic pathways that require energy in the form of ATP and NAD (P) H to achieve high production rates, ie as opposed to the thermodynamically ‘downhill’catabolic metabolic pathways used to produce ethanol (or butanol or short-chain carboxylic acids) by anaerobic fermentation, which are net ATP-positive, redox balanced, and can be performed anaerobically. The use of metabolic pathways requiring aerobic respiration to generate the energy needed to drive them, while reasonable for producing high-value fine chemicals, therapeutics, amino acids, antibiotics, and even some higher value commodity chemicals, poses serious challenges for economic production of huge-volume, lower cost fuels. This is primarily due to the additional capital and operating costs required to supply oxygen (O2) to a submerged culture and secondarily due to reduced economies of scale for scaling up aerobic versus anaerobic processes. As an example, the higher costs for aerobic …