Martínez Henar, Santos Mercedes, Pedraza Lucía, Testera Ana M
Department of Organic Chemistry, School of Engineering (EII), University of Valladolid (UVa), Dr. Mergelina, 47002 Valladolid, Spain.
G.I.R. Computational Chemistry Group, Department of Physical Chemistry and Inorganic Chemistry, Science Faculty, University of Valladolid (UVa), Paseo de Belén 7, 47011 Valladolid, Spain.
Mar Drugs. 2025 Feb 7;23(2):69. doi: 10.3390/md23020069.
Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain the only alternative to producing these compounds on an industrial scale. Their supply can often be implemented with laboratory scale cultures for bacterial, fungal, or microalgal sources. However, a diverse approach, combining traditional methods with modern synthetic biology and biosynthesis strategies, must be considered for invertebrate MNPs, as they are usually naturally accumulated in only very small quantities. This review offers a comprehensive examination of various production strategies for MNPs, addressing the challenges related to supply, synthesis, and scalability. It also underscores recent biotechnological advancements that are likely to transform the current industrial-scale manufacturing methods for pharmaceuticals derived from marine sources.
海洋生物是独特化学实体的来源,具有宝贵的生物医学潜力、广泛的多样性和复杂性。确保可靠且可持续地供应海洋天然产物(MNPs),以便将其转化为商业药物和其他有价值的产品至关重要。从结构角度来看,除少数例外,具有药物重要性的MNPs源自海洋生物的所谓次生代谢。当生产策略依赖海洋大型生物时,收获或培养并结合提取程序通常仍是在工业规模上生产这些化合物的唯一选择。对于细菌、真菌或微藻来源,其供应通常可以通过实验室规模的培养来实现。然而,对于无脊椎动物的MNPs,必须考虑采用一种将传统方法与现代合成生物学和生物合成策略相结合的多样化方法,因为它们通常仅以非常少量自然积累。本综述全面审视了MNPs的各种生产策略,探讨了与供应、合成和可扩展性相关的挑战。它还强调了近期的生物技术进展,这些进展可能会改变目前源自海洋的药物的工业规模制造方法。