Polycyclic tetramate macrolactams (PoTeMs) are a growing class of natural products with distinct structure and diverse biological activities. By promoter engineering and heterologous expression of the cryptic cbm gene cluster, four new PoTeMs, combamides A-E (1-4), were identified. Additionally, two new derivatives, combamides E (5) and F (6), were generated via combinatorial biosynthesis. Together, our findings provide a sound base for expanding the structure diversities of PoTeMs through genome mining and combinatorial biosynthesis.

Five new polyketides of the ansamycin class, named ansavaricins A–E (1–5), together with three known streptovaricins 6–8, were isolated from the Streptomyces sp. S012 strain.

Flavin-dependent halogenases (FDHs) are known for installing halogens on natural products. To date, most reported FDHs are two-component FDHs, which require a flavin reductase as the reaction partner to function. Here, we report the identification of a new halogenated biaryl compound 2-chloro venemycin (1) through constitutive expression of the regulator gene vemR in the vem gene cluster in Streptomyces sp. S006 and media optimization. In addition, we provide biochemical evidence that, in the absence of the flavin reductase, purified FDH VemK catalyzes the regioselective halogenation of the pyrone moiety of venemycin (2). Mutagenesis studies showed that T315 and R317 residues are likely crucial for catalysis and NAD­(P)H binding. VemK represents the first characterized single-component FDH from Streptomyces and the first FDH that halogenates a pyrone moiety.

Ansamycins are a family of macrolactams characterized by an aromatic chromophore with an aliphatic chain (ansa chain) connected back to a nonadjacent position through an amide bond. In this study, four new polyketides of ansamycin class, designated as ansavaricins F-I (1-4), were obtained from the Streptomyces sp. S012 strain. All the compounds were structurally characterized as open-chain streptovaricin derivatives by using NMR and HRESIMS techniques, and showed different degrees of inhibition against human DNA topoisomerases. Ansavaricin H is a promising lead for the development of new inhibitors of human DNA topoisomerases.

Four new dinorsesterterpenoids, designated as trinulactones A–D (1–4), were isolated from the Streptomyces sp. S006 strain. All the compounds contained a tricyclic skeleton, which was attached to a highly oxygenated unsaturated γ-lactone. Their structures were determined by analysis of their spectroscopic data, mainly 1D, 2D NMR and HR-ESIMS data. In particular, compounds 3a/3b and 4a/4b were identified individually as atropisomers.