2,2'-联二吡啶能与金属离子稳定螯合，在金属有机化学等领域应用广泛。针对这类化合物有机合成的方法学研究较为成熟，主要以相同或不同取代的吡啶单元通过金属介导的偶联反应实现。在自然界中存在着大量以2,2'-联二吡啶为核心骨架的天然产物，然而对于其生物合成途径的了解并不深入。在本项目中，我们以结构上具有代表性的青蓝霉素（CAEs）和克里斯霉素（COLs）为研究对象，研究这两类化合物如何以小分子羧酸和氨基酸为前体，通过"非典型"的聚酮合酶（PKS）和非核糖体肽合成酶（NRPS）催化核心骨架的组装逻辑。我们将结合体内、体外相关实验揭示以CAEs和COLs为代表的抗生素生物合成的共性和个性，明确CAEs和COLs相同的联二吡啶环形成机制、以及二者不同的骨架形成后修饰的成因。研究成果将拓宽人们对PKS和NRPS催化反应的认识，填补对脱硫机制认识的空白，同时推进以联二吡啶类结构为基础的新分子的生物创制。

The ligand 2,2'-bipyridine, capable of chelating and stablizating metal ions, is widely applied in various areas including that of organometallic chemistry. The methodology regarding the chemical synthesis of 2,2'-bipyridine-containing compounds has been well-developed, primarily based on the metal-mediated homo- or cross-coupling of two pyridines. There are a large number of natural products containing the 2,2'-bipyridine core scaffold; however, their biosynthetic routes have been poorly understood. In this project, we choose the structurally representative 2,2'-bipyridine natural products, caerulomycins (CAEs) and collismycins (COLs), as the target molecules, to access the biosynthetic logic how an "atypical" polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) hybrid system programs the formation of the 2,2'-bipyridine core. According to the in vivo and in vitro experiments, we aim to characterize the generality in the CAE or COL-represented 2,2'-bipyridine formation and the specificity in their post-scaffold modifications. The findings in this project will expand the understanding in PKS and/or NRPS-catalyzed reactions, fill the knowledge gap regarding desulfurization mechanism, and motivate the biosynthesis of new organic small molecules that harbor the 2,2'-bipyridine core.