Activating a Cryptic Ansamycin Biosynthetic Gene Cluster To Produce Three New Naphthalenic Octaketide Ansamycins with <i>n</i>‑Pentyl and <i>n</i>‑Butyl Side Chains

Genome mining is a rational approach to discovering new natural products. The genome sequence analysis of <i>Streptomyces</i> sp. LZ35 revealed the presence of a putative ansamycin gene cluster (<i>nam</i>). Constitutive overexpression of the pathway-specific transcriptional regulatory gene <i>nam1</i> successfully activated the <i>nam</i> gene cluster, and three novel naphthalenic octaketide ansamycins were discovered with unprecedented <i>n</i>-pentylmalonyl-CoA or <i>n</i>-butylmalonyl-CoA extender units. This study represents the first example of discovering novel ansamycin scaffolds via activation of a cryptic gene cluster

Juanlimycins A and B, Ansamycin Macrodilactams from <i>Streptomyces</i> sp.

Ansamycins are a family of macrolactams characterized by an aromatic chromophore with an aliphatic chain (<i>ansa</i> chain) connected back to a nonadjacent position through an amide bond. This family has shown a high degree of druggability exemplified by rifamycins, maytansinoids, and geldanamycins. In this study, the isolation of two novel ansamycin macrodilactams with unprecedented features, juanlimycins A (<b>1</b>) and B (<b>2</b>), from <i>Streptomyces</i> sp. LC6 were reported. The structures of <b>1</b> and <b>2</b> were assigned on the basis of analysis of NMR spectroscopic data and X-ray single crystal diffraction