Bombyxamycins A and B, Cytotoxic Macrocyclic Lactams from an Intestinal Bacterium of the Silkworm Bombyx mori

Abstract

Bombyxamycins A and B (1 and 2) were discovered from a silkworm gut Streptomyces bacterium. Spectroscopic analysis and multiple-step chemical derivatization identified them as 26-membered cyclic lactams with polyene features. Bombyxamycin A showed significant antibacterial and antiproliferative effects. The bombyxamycin biosynthetic gene cluster was identified by genetic analysis. Gene deletion experiments confirmed that the cytochrome P450 BomK is responsible for the generation of 2, which unprecedentedly bears tetrahydrofuran in its macrocyclic ring.

Novel Macrolactams from a Deep-Sea-Derived Streptomyces Species

“…Analysis of its COSY correlations of H-8/H-9/H-14/H-15 revealed the presence of a fourmembered ring system that was fused with a six-membered ring, which was confirmed by the COSY correlations of H-10/H-11/H-12 and the key HMBC correlations of H-9 to C-10/C-11/C-13, H-12 to C-14, and H-14 to C-13/C-15/C-16 (Figure 3). The fused [20,4,6] assigned by HSQC (Figure S9), indicated the presence of twelve olefinic carbons, three carbonyl groups (δC 166.3 for amide carbonyl signal; δC 194.8 and 213.1 for keto carbonyl signals), eight sp -methine groups including three oxygenated carbons, two methylene groups, and three methyl groups. Analysis of its COSY correlations of H-8/H-9/H-14/H-15 revealed the presence of a four-membered ring system that was fused with a six-membered ring, which was confirmed by the COSY correlations of H-10/H-11/H-12 and the key HMBC correlations of H-9 to C-10/C-11/C-13, H-12 to C-14, and H-14 to C-13/C-15/C-16 (Figure 3).…”

“…Analysis of its COSY correlations of H-8/H-9/H-14/H-15 revealed the presence of a four-membered ring system that was fused with a six-membered ring, which was confirmed by the COSY correlations of H-10/H-11/H-12 and the key HMBC correlations of H-9 to C-10/C-11/C-13, H-12 to C-14, and H-14 to C-13/C-15/C-16 (Figure 3). The fused [20,4,6] tricyclic framework was determined by the key COSY correlations of H-4/H-5, H-7/H-8, H-15/H-16/H-17, H-24/H3-28, and extending from H-19 to H2-25, and the key HMBC correlations of NH to C-1, H-2 to C-1/C-3, H-4 to C-3/C-6, H-5 to C-3/C-7, H3-26 to C-5/C-6/C-7, and H3-27 to C-17/C-18/C-19 (Figure 3). This structure was deduced to form from the intramolecular [2 + 2] cycloaddition of compound 1.…”

“…Macrolactams isolated from actinobacteria have become a large family of natural products, which showed lots of different biological activities and received more and more attention [1][2][3][4]. Some molecules with novel macrolactam frameworks and significant activities have been isolated from various actinobacterial strains, such as dracolactams [5], bombyxamycins [6], macrotermycins [7], verticilactam [8], sceliphrolactam [9], tripartilactam [10], and niizalactam C (4) [11]. The structure of tripartilactam has been revised to be the same as niizalactam C (4) [12].…”

“…The structure of tripartilactam has been revised to be the same as niizalactam C (4) [12]. It possesses a fused [18,6,6]-tricyclic system, which was proposed to be formed from sceliphrolactam via a spontaneous intramolecular [4 + 2] cycloaddition [12].…”

“…As a result, three novel macrolactams, streptolactams A-C (1-3), together with the reported niizalactam C (4) [11] (Figure 1), were isolated and identified. Structurally, streptolactam A (1) is a 26-membered cyclic polyene macrolactam [9], Structurally, streptolactam A (1) is a 26-membered cyclic polyene macrolactam [9], while streptolactam B (2) possesses a novel [20,4,6]-fused tricyclic skeleton, and streptolactam C (3) has an 11,23-oxgen bridged [14,16] bicyclic system. Herein, we reported the isolation, cytotoxic and antimicrobial activity, as well as the complete structural elucidation of compounds 1-4.…”