Liu Dake, Rubin Garret M, Dhakal Dipesh, Chen Manyun, Ding Yousong
Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA.
iScience. 2021 May 4;24(5):102512. doi: 10.1016/j.isci.2021.102512. eCollection 2021 May 21.
Peptidic natural products (PNPs) represent a rich source of lead compounds for the discovery and development of therapeutic agents for the treatment of a variety of diseases. However, the chemical synthesis of PNPs with diverse modifications for drug research is often faced with significant challenges, including the unavailability of constituent nonproteinogenic amino acids, inefficient cyclization protocols, and poor compatibility with other functional groups. Advances in the understanding of PNP biosynthesis and biocatalysis provide a promising, sustainable alternative for the synthesis of these compounds and their analogues. Here we discuss current progress in using native and engineered biosynthetic enzymes for the production of both ribosomally and nonribosomally synthesized peptides. In addition, we highlight new and approaches for the generation and screening of PNP libraries.
肽类天然产物（PNPs）是用于发现和开发治疗多种疾病的治疗药物的丰富先导化合物来源。然而，用于药物研究的具有多种修饰的PNPs的化学合成常常面临重大挑战，包括组成性非蛋白质氨基酸的不可用性、低效的环化方案以及与其他官能团的兼容性差。对PNP生物合成和生物催化理解的进展为这些化合物及其类似物的合成提供了一种有前景的、可持续的替代方法。在这里，我们讨论了使用天然和工程化生物合成酶生产核糖体合成和非核糖体合成肽的当前进展。此外，我们强调了生成和筛选PNP文库的新方法和途径。
