Butkovich Lazarina V, Vining Oliver B, O'Malley Michelle A
Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA.
Appl Microbiol Biotechnol. 2025 Jan 20;109(1):12. doi: 10.1007/s00253-024-13393-y.
The animal gut microbiome is a complex system of diverse, predominantly anaerobic microbiota with secondary metabolite potential. These metabolites likely play roles in shaping microbial community membership and influencing animal host health. As such, novel secondary metabolites from gut microbes hold significant biotechnological and therapeutic interest. Despite their potential, gut microbes are largely untapped for secondary metabolites, with gut fungi and obligate anaerobes being particularly under-explored. To advance understanding of these metabolites, culture-based and (meta)genome-based approaches are essential. Culture-based approaches enable isolation, cultivation, and direct study of gut microbes, and (meta)genome-based approaches utilize in silico tools to mine biosynthetic gene clusters (BGCs) from microbes that have not yet been successfully cultured. In this mini-review, we highlight recent innovations in this area, including anaerobic biofoundries like ExFAB, the NSF BioFoundry for Extreme & Exceptional Fungi, Archaea, and Bacteria. These facilities enable high-throughput workflows to study oxygen-sensitive microbes and biosynthetic machinery. Such recent advances promise to improve our understanding of the gut microbiome and its secondary metabolism. KEY POINTS: • Gut microbial secondary metabolites have therapeutic and biotechnological potential • Culture- and (meta)genome-based workflows drive gut anaerobe metabolite discovery • Anaerobic biofoundries enable high-throughput workflows for metabolite discovery.
动物肠道微生物群是一个由多样的、主要为厌氧的微生物群组成的复杂系统，具有产生次生代谢产物的潜力。这些代谢产物可能在塑造微生物群落组成和影响动物宿主健康方面发挥作用。因此，来自肠道微生物的新型次生代谢产物具有重大的生物技术和治疗意义。尽管具有潜力，但肠道微生物在次生代谢产物方面大多未被开发利用，肠道真菌和专性厌氧菌尤其未得到充分研究。为了增进对这些代谢产物的了解，基于培养和（宏）基因组的方法至关重要。基于培养的方法能够分离、培养和直接研究肠道微生物，而基于（宏）基因组的方法则利用计算机工具从尚未成功培养的微生物中挖掘生物合成基因簇（BGCs）。在本综述中，我们重点介绍了该领域的最新创新成果，包括像ExFAB这样的厌氧生物铸造厂、美国国家科学基金会的极端与特殊真菌、古菌和细菌生物铸造厂。这些设施能够实现高通量工作流程，以研究对氧气敏感的微生物和生物合成机制。这些最新进展有望增进我们对肠道微生物群及其次生代谢的理解。要点：• 肠道微生物次生代谢产物具有治疗和生物技术潜力 • 基于培养和（宏）基因组的工作流程推动肠道厌氧菌代谢产物的发现 • 厌氧生物铸造厂能够实现高通量代谢产物发现工作流程
