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羊毛硫肽:化学合成与体内生物合成作为药物生产工具的比较

Lanthipeptides: chemical synthesis versus in vivo biosynthesis as tools for pharmaceutical production.

作者信息

Ongey Elvis Legala, Neubauer Peter

机构信息

Chair of Bioprocess Engineering, Department of Biotechnology, Technische Universität Berlin, Ackerstraße 76, ACK24, 13355, Berlin, Germany.

出版信息

Microb Cell Fact. 2016 Jun 7;15:97. doi: 10.1186/s12934-016-0502-y.

DOI:10.1186/s12934-016-0502-y
PMID:27267232
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4897893/
Abstract

Lanthipeptides (also called lantibiotics for those with antibacterial activities) are ribosomally synthesized post-translationally modified peptides having thioether cross-linked amino acids, lanthionines, as a structural element. Lanthipeptides have conceivable potentials to be used as therapeutics, however, the lack of stable, high-yield, well-characterized processes for their sustainable production limit their availability for clinical studies and further pharmaceutical commercialization. Though many reviews have discussed the various techniques that are currently employed to produce lanthipeptides, a direct comparison between these methods to assess industrial applicability has not yet been described. In this review we provide a synoptic comparison of research efforts on total synthesis and in vivo biosynthesis aimed at fostering lanthipeptides production. We further examine current applications and propose measures to enhance product yields. Owing to their elaborate chemical structures, chemical synthesis of these biomolecules is economically less feasible for large-scale applications, and hence biological production seems to be the only realistic alternative.

摘要

羊毛硫肽(对于具有抗菌活性的那些而言也称为羊毛硫抗生素)是核糖体合成的、具有硫醚交联氨基酸(羊毛硫氨酸)作为结构元件的翻译后修饰肽。羊毛硫肽具有用作治疗剂的潜在可能性,然而,缺乏用于其可持续生产的稳定、高产、特性良好的工艺限制了它们用于临床研究和进一步药物商业化的可用性。尽管许多综述已经讨论了目前用于生产羊毛硫肽的各种技术,但尚未描述这些方法之间为评估工业适用性而进行的直接比较。在本综述中,我们对旨在促进羊毛硫肽生产的全合成和体内生物合成的研究工作进行了概要比较。我们进一步研究了当前的应用并提出了提高产品产量的措施。由于其复杂的化学结构,这些生物分子的化学合成在大规模应用中在经济上不太可行,因此生物生产似乎是唯一现实的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/8445b9e6d284/12934_2016_502_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/932ea7f87722/12934_2016_502_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/dcf348a8deb6/12934_2016_502_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/2649b5ee65b7/12934_2016_502_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/cfe1f2748136/12934_2016_502_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/625bb8f3e82d/12934_2016_502_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/8445b9e6d284/12934_2016_502_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/932ea7f87722/12934_2016_502_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/dcf348a8deb6/12934_2016_502_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/2649b5ee65b7/12934_2016_502_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/cfe1f2748136/12934_2016_502_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/625bb8f3e82d/12934_2016_502_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8e/4897893/8445b9e6d284/12934_2016_502_Fig6_HTML.jpg

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