SusChEM: Time-series Characterization and Modeling of Non-model Microalgae at the Systems-level for Sustainable Chemical Production

Pi姓名：Gunes E.Atilla-GokumenNumber：1438172 21世纪工程学的重大挑战之一是提供可持续和经济可行的商品产品，同时缓解人口增加、全球气候变化和有限的自然资源的压力。一种看似合理的办法是，在长期适应和缓解战略中利用能够满足上述许多标准的可再生原料。为此，微藻可以有效地将阳光和二氧化碳转化为高价值的产品，如生物燃料、营养补充剂和治疗剂。然而，微藻生物燃料和可持续化学生产的全球细胞代谢过程还没有被很好地理解。该项目将开发基础和应用的工程工具和指标，以更好地了解如何利用光合作用有机体生产在能源、健康和食品工业中应用的高价值产品。通过基于微藻的过程进行可持续燃料和化学品生产这一主题具有引人注目的广泛社会影响，这些主题将通过与拟议研究相结合的学术和公民参与活动进行交流。在微藻中，几个复杂和相互关联的内部机制决定了碳氢化合物的生物合成、降解，并最终决定了其积累的前景。事实上，初步数据表明，微藻缺乏营养等应激条件不仅会触发脂类和萜类的生物合成，还会上调溶酶体和过氧化物体中负责脂类降解的几种酶的表达。将研究合成代谢反应和分解代谢反应的表达和相互作用之间的关系，以最大限度地促进烃的形成，这将扩大目前对微藻中烃的生物合成的理解。更具体地说，为了最大限度地提高二氧化碳固定效率和类脂和萜类化合物的积累，将采用全面的实验和理论方法来了解非模型含油微藻的基本代谢和改善最终代谢产物的生产指标。在这项工作中，油藻新氯藻将在不同的氮和磷营养水平下生长，并按时间序列进行采样，用于转录和代谢分析，旨在表征和优化类脂和萜类化合物的形成。稳态和动态化学计量代谢模型将被用来确定和预测系统水平对临界底物吸收速率和胁迫诱导的合成和分解代谢基因活性的响应，因为它们与最大限度地积累脂肪和萜类化合物有关。同时，将采用诱变和高分辨率筛选设计，以进一步改进非模型微藻生产指标，更重要的是，为代表改善碳氢化合物生产的所有三个目标提供一个比较基础。

PI Name: Gunes E. Atilla-GokcumenNumber: 1438172One of the grand challenges of engineering in the 21st century is to provide sustainable and economically-viable commodity products while easing the pressure of population increase, global climate change, and limited natural resources. One plausible approach is to utilize renewable feedstocks that can accommodate these many criteria in long-term adaption and mitigation strategies. Towards this end, microalgae can efficiently convert sunlight and carbon dioxide into high-value products such as biofuels, nutritional supplements, and therapeutic agents. However, the global cellular metabolic processes underlying biofuel and sustainable chemical production from microalgae are not well understood. This project will develop fundamental and applied engineering tools and metrics to better understand how photosynthetic organisms can be exploited to produce high-value products with applications in energy, health, and food industries. The theme of sustainable fuel and chemical production through microalgae-based processes has compelling broad societal impacts, and these topics will be communicated through academic and civic engagement activities that are integrated with the proposed research.Technical Description In microalgae, several complex and linked internal mechanisms dictate hydrocarbon biosynthesis, degradation, and, ultimately, the prospect for their accumulation. In fact, preliminary data suggests stress conditions such as nutrient deprivation in microalgae not only trigger lipid and terpenoid biosynthesis but also up-regulate several enzymes responsible for lipid degradation in lysosomes and peroxisomes. The relationship between the expression and interaction of anabolic and catabolic reactions will be investigated with the goal of maximizing hydrocarbon formation that will extend the current understanding of hydrocarbon biosynthesis in microalgae. More specifically, in order to maximize carbon dioxide fixation efficiency and lipid and terpenoid accumulation, a comprehensive experimental and theoretical approach will be employed to understand basic metabolism and improve final metabolite production metrics in non-model oleaginous microalgae. In this work, the microalga Neochloris oleoabundans will be grown under varying nitrogen and phosphorous nutrient levels, and sampled in time-series for transcriptomic and metabolomic analyses designed to characterize and optimize lipid and terpenoid formation. Steady state and dynamic stoichiometric metabolic modeling will be used to determine and predict systems-level responses to critical substrate uptake rates and stress-induced anabolic and catabolic gene activity as they pertain to maximized lipid and terpenoid accumulation. In parallel, a mutagenesis and high-resolution screening design will be applied to further improve non-model microalgae production metrics and, more importantly, provide a comparative basis across all three aims for intracellular metabolism representative of improved hydrocarbon production.