Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez 2, 38206 La Laguna, Spain.
Departamento de Química Orgánica, Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez 2, 38206 La Laguna, Spain.
Mar Drugs. 2021 Jul 29;19(8):432. doi: 10.3390/md19080432.
The demand for valuable products from dinoflagellate biotechnology has increased remarkably in recent years due to their many prospective applications. However, there remain many challenges that need to be addressed in order to make dinoflagellate bioactives a commercial reality. In this article, we describe the technical feasibility of producing and recovering amphidinol analogues (AMs) excreted into a culture broth of ACRN03, successfully cultured in an LED-illuminated pilot-scale (80 L) bubble column photobioreactor operated in fed-batch mode with a pulse feeding strategy. We report on the isolation of new structurally related AMs, amphidinol 24 (, AM24), amphidinol 25 (, AM25) and amphidinol 26 (, AM26), from a singular fraction resulting from the downstream processing. Their planar structures were elucidated by extensive NMR and HRMS analysis, whereas the relative configuration of the C-32→C-47 bis-tetrahydropyran core was confirmed to be antipodal in accord with the recently revised configuration of AM3. The hemolytic activities of the new metabolites and other related derivatives were evaluated, and structure-activity conclusions were established. Their isolation was based on a straightforward and high-performance bioprocess that could be suitable for the commercial development of AMs or other high-value compounds from shear sensitive dinoflagellates.
近年来，由于具有许多潜在的应用前景，对甲藻生物技术中高价值产品的需求显著增加。然而，为了使甲藻生物活性物质成为商业现实，仍有许多挑战需要解决。在本文中，我们描述了在 LED 照明的中试规模（80L）鼓泡塔式光生物反应器中成功培养 ACRN03 的条件下，从培养物中分泌的拟 Amphidinol 类似物（AMs）进行生产和回收的技术可行性，该生物反应器采用脉冲进料策略在分批补料模式下运行。我们报告了从单一馏分中分离出新的结构相关的 AMs，即 amphidinol 24 (, AM24)、amphidinol 25 (, AM25) 和 amphidinol 26 (, AM26)，该馏分来自下游处理。通过广泛的 NMR 和 HRMS 分析阐明了它们的平面结构，而 C-32→C-47 双四氢吡喃核心的相对构型被确认为与最近修订的 AM3 构型相反。评估了新代谢物和其他相关衍生物的溶血活性，并建立了结构活性结论。它们的分离基于一种简单且高效的生物工艺，该工艺可能适用于 AMs 或其他来自剪切敏感甲藻的高价值化合物的商业开发。
