Schwarzer Dirk, Finking Robert, Marahiel Mohamed A
Philipps-Universität Marburg, Fachbereich Chemie/Biochemie, Hans-Meerwein-Strasse, 35043 Marburg, Germany.
Nat Prod Rep. 2003 Jun;20(3):275-87. doi: 10.1039/b111145k.
The ability to synthesize nonribosomally small bioactive peptides that find application in modern medicine is widely spread among microorganisms. As broad as the spectrum of biological activities is the structural diversity of these peptides, which are mostly cyclic or branched cyclic compounds containing non-proteinogenic amino acids, small heterocyclic rings and other unusual modifications in the peptide backbone. They are synthesized by multimodular enzymes, the so-called nonribosomal peptide synthetases (NRPSs), from simple building blocks. Biochemical and genetic studies have unveiled the key principles of nonribosomal peptide syntheses, as well as the realization of many structural features of these peptides. This review focuses on recent results in NRPS research and highlights how this knowledge can be exploited for biotechnological purposes. In addition, possibilities and limitations for prediction of structural features of uncharacterized NRPSs and approaches for their engineering are discussed.
能够合成在现代医学中具有应用价值的非核糖体小生物活性肽的能力在微生物中广泛存在。这些肽的结构多样性与生物活性谱一样广泛，它们大多是含有非蛋白质氨基酸、小杂环和肽主链中其他异常修饰的环状或支链环状化合物。它们由多模块酶，即所谓的非核糖体肽合成酶（NRPSs），从简单的构建模块合成。生化和遗传学研究揭示了非核糖体肽合成的关键原理，以及这些肽的许多结构特征的实现方式。本综述重点关注NRPS研究的最新成果，并强调如何将这些知识用于生物技术目的。此外，还讨论了预测未表征NRPSs结构特征的可能性和局限性及其工程改造方法。
