Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
J Am Chem Soc. 2012 Apr 25;134(16):6952-5. doi: 10.1021/ja3017297. Epub 2012 Apr 11.
Ribosomally synthesized and post-translationally modified peptides are a rapidly expanding class of natural products. They are typically biosynthesized by modification of a C-terminal segment of the precursor peptide (the core peptide). The precursor peptide also contains an N-terminal leader peptide that is required to guide the biosynthetic enzymes. For bioengineering purposes, the leader peptide is beneficial because it allows promiscuous activity of the biosynthetic enzymes with respect to modification of the core peptide sequence. However, the leader peptide also presents drawbacks as it needs to be present on the core peptide and then removed in a later step. We show that fusing the leader peptide for the lantibiotic lacticin 481 to its biosynthetic enzyme LctM allows the protein to act on core peptides without a leader peptide. We illustrate the use of this methodology for preparation of improved lacticin 481 analogues containing non-proteinogenic amino acids.
核糖体合成和翻译后修饰肽是一类迅速扩张的天然产物。它们通常通过对前体肽（核心肽）的 C 末端片段进行修饰来生物合成。前体肽还包含一个 N 末端引导肽，该肽对于引导生物合成酶是必需的。出于生物工程的目的，该引导肽是有益的，因为它允许生物合成酶对核心肽序列进行修饰的混杂活性。然而，该引导肽也存在缺点，因为它需要存在于核心肽上，然后在后续步骤中被去除。我们表明，将类细菌素乳链菌肽 481 的引导肽与其生物合成酶 LctM 融合，可使该蛋白在没有引导肽的情况下作用于核心肽。我们说明了该方法在制备含有非蛋白氨基酸的改良乳链菌肽 481 类似物中的应用。
