Collaborative Research: Probing Active Fraction and Metabolic Function to Elucidate Mechanisms of Pharmaceutical Biotransformations during Nitrification-Denitrification

1438578 Chandran1438221 Ramsburg近年来，微量成分的广泛存在和对环境的影响越来越受到关注。一类重要的微量成分是具有药物活性的化合物。越来越多的证据表明，长期接触具有药物活性的化合物，即使在极低的浓度下，也可能对生态系统产生不利影响，如胚胎发育受损、鱼类的摄食和社会行为改变、藻类的生长抑制和呼吸减少。虽然其中一些影响是可逆的，但其他的解剖学、生理学和遗传学改变是永久性的。因此，评估、理解和减轻药物活性化合物和更广泛的微量成分对环境的有害影响是环境工程和科学界面临的重大挑战之一。目前研究药用活性化合物在生物废水处理中去向的方法普遍缺乏机械基础，因此不能明确指出在去除药用活性化合物方面起作用的主要微生物群落和代谢途径。这导致对活性物种的身份和关键的衰减过程缺乏共识。为了解开复杂性和现场特定结果的难题，PI提出了一种了解药物活性化合物命运的基本方法--一种可以指导未来研究和实施工作的方法。该项目旨在对活性污泥中负责转化和去除药用活性化合物的微生物“活性部分”有一个清晰的了解，并阐明其组成代谢途径。第二个目标是量化和区分与生长相关的(与合成代谢有关的)和与非生长相关的(与分解代谢或偶然反应有关的)药物活性化合物的转化和降解。了解微生物作用于新出现的令人关注的污染物的相互作用，对于应对目前水质研究人员和专业人员面临的科学挑战至关重要。研究中提出的理解这些过程的方法可能会为未来旨在了解整个环境中的生物降解机制的科学研究奠定基础。环境中存在的低浓度人为化学混合物的影响是21世纪科学家和工程师面临的巨大挑战之一。有效的废水处理对保持水质至关重要，但传统上被认为有效的水处理可能还需要包括微量成分--这些设施从未专门设计用于处理的化合物。这项研究将进一步发展和应用先进的微生物生态技术，以揭示活性污泥中的细菌如何与具有药用活性的化合物相互作用。通过这些最先进的分子工具实现的高级理解可以扩展到询问不同活性污泥配置中的药物活性化合物新陈代谢。此外，对活性成分和代谢途径的了解有助于改进标准化方案，这些方案可用于未来的研究，以估计现有的生物动力学参数，并为药物活性化合物的去除构建更准确的预测模型。从根本上讲，到目前为止还没有代谢模型可以描述药物活性化合物的降解途径。这可能是由于缺乏与了解具有药用活性的化合物在混合细菌群落中生物降解的机制有关的详细研究。作为该项目的一部分，私人投资促进机构建议开发这样一个模型并将其参数化。

1438578Chandran1438221RamsburgThe widespread occurrence and environmental impacts of microconstituents has received increasing attention in recent years. An important class of microconstituents is pharmaceutically active compounds. There is a growing body of evidence that suggests chronic exposure to pharmaceutically active compounds, even at extremely low concentrations could have adverse effects on ecosystems, such as impaired embryo development, modified feeding and social behavior of fish, suppression of growth and reduction in respiration in algae. While some of these effects are reversible, other anatomical, physiological, and genetic alterations are permanent. Thus, the challenge of assessing, understanding, and mitigating the deleterious influence of pharmaceutically active compounds, and microconstituents more broadly, on the environment is one of the great challenges facing the environmental engineering and science community. Current approaches to study pharmaceutically active compounds fate in biological wastewater treatment generally lack a mechanistic basis and therefore cannot unambiguously pinpoint the protagonist microbial communities and metabolic pathways that are active in the removal of pharmaceutically active compounds. This leads to a lack of consensus regarding the identity of active species and critical attenuation processes. To unravel the conundrum of complexity and site specific results, the PIs propose a fundamental approach to understanding the fate of pharmaceutically active compounds - one that can guide future research and implementation efforts. This project aims to develop a clear understanding of the microbial "active fraction" in activated sludge which is responsible for the transformation and removal of pharmaceutically active compounds, and to elucidate the constituent metabolic pathways. A secondary objective is to quantify and differentiate between growth associated (linked to anabolism) and non-growth associated (linked to catabolism or fortuitous reactions) pharmaceutically active compounds transformation and degradation. Understanding the interplay of microbial processes acting on contaminants of emerging concern is critical to meeting the scientific challenges now facing water quality researchers and professionals. The approach to understanding these processes offered in the proposed research may seed future scientific investigations aimed at understanding biodegradation mechanisms throughout the environment.The influence of anthropogenic chemical mixtures present within the environment at low concentration is one of the great challenges facing scientists and engineers in the 21st century. Effective wastewater treatment is critical to maintaining water quality, but what is traditionally thought of as effective may need to also include microconstituents - compounds that these facilities were never specifically designed to treat. This study will further the development and application of advanced microbial-ecological techniques to shed new light on how bacteria within activated sludge interact with pharmaceutically active compounds. The advanced understanding enabled by these state-of-the-art molecular tools can be extended to interrogate pharmaceutically active compound metabolism in different activated sludge configurations. Further, the knowledge of the "active fraction" and metabolic pathways can help improve standardized protocols that can be used by future studies to estimate the extant biokinetic parameters and to construct more accurate predictive models for pharmaceutically active compounds removal. From a fundamental perspective, there is no metabolic model to date, that can describe pharmaceutically active compounds degradation pathways. This is possibly due to a lack of detailed studies related to understanding the mechanisms by which pharmaceutically active compounds are biodegraded within mixed communities of bacteria. As part of this project, the PIs propose to develop and parameterize such a model.