Univ. Angers, Univ. Brest, GEIHP, SFR ICAT, F-49000 Angers, France.
School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Biotechnol Adv. 2022 Jan-Feb;54:107871. doi: 10.1016/j.biotechadv.2021.107871. Epub 2021 Nov 19.
The marine environment is a huge reservoir of biodiversity and represents an excellent source of chemical compounds, some of which have large economical values. In the urgent quest for new pharmaceuticals, marine-based drug discovery has progressed significantly over the past several decades and we now benefit from a series of approved marine natural products (MNPs) to treat cancer and pain while an additional collection of promising leads are in clinical trials. However, the discovery and supply of MNPs has always been challenging given their low bioavailability and structural complexity. Their manufacture for pre-clinical and clinical development but also commercialization mainly relies upon marine source extraction and chemical synthesis, which are associated with high costs, unsustainability and severe environmental problems. In this review, we discuss how metabolic engineering now raises reasonable expectations for the implementation of microbial cell factories, which may provide a sustainable approach for MNP-based drug supply in the near future.
海洋环境是生物多样性的巨大宝库,也是化合物的绝佳来源,其中一些化合物具有巨大的经济价值。在迫切需要新药的情况下,过去几十年来,基于海洋的药物发现取得了重大进展,我们现在受益于一系列已批准的海洋天然产物 (MNPs) 来治疗癌症和疼痛,同时还有一系列有前途的先导化合物正在临床试验中。然而,由于 MNPs 的生物利用度低和结构复杂,它们的发现和供应一直具有挑战性。它们的制造用于临床前和临床开发,以及商业化主要依赖于海洋来源的提取和化学合成,这与高成本、不可持续性和严重的环境问题有关。在这篇综述中,我们讨论了代谢工程如何为微生物细胞工厂的实施带来合理的期望,这可能为未来基于 MNPs 的药物供应提供一种可持续的方法。