Fig. 5.

Nature’s combinatorial biosynthesis for the LNM family of natural products. (A) The LNM-type biosynthetic machineries, featuring a hybrid NRPS–AT–less type I PKS with varying substrate specificity and modification domains, to account for the structural diversity found within the LNM family of natural products. Domains marked with red dotted circles vary among the machineries. Gaps between domains denote protein boundaries, with red dotted lines denoting that the two domains (enzymes) are fused in some of the machineries. (B) A composite structure depicting varying features of the LNM family of natural products that could be correlated with different modules shown with colored squares. Those marked with asterisks denote the structural motifs that have been discovered from the structures of LNMs, GNMs, and WSMs. (C) A mosaic view of the structural diversity of the LNM family of natural products, highlighting Nature’s intrinsic use of combinatorial biosynthesis. The roman numerals (I–V, VII–XVIII) represent the 17 different clades of potential producers of LNM-type natural products (Fig. 2A).