Baikalomycins A-C, New Aquayamycin-Type Angucyclines Isolated from Lake Baikal Derived Streptomyces sp. IB201691-2A

Abstract

Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis. In the course of an activity guided screening three new angucyclines, named baikalomycins A–C, were isolated and characterized, highlighting the potential of poorly investigated ecological niches. Besides that, the strain was found to accumulate large quantities of rabelomycin and 5-hydroxy-rabelomycin, known shunt products in angucyclines biosynthesis. Baikalomycins A–C demonstrated varying degrees of anticancer activity. Rabelomycin and 5-hydroxy-rabelomycin further demonstrated antiproliferative activities. The structure elucidation showed that baikalomycin A is a modified aquayamycin with β-d-amicetose and two additional hydroxyl groups at unusual positions (6a and 12a) of aglycone. Baikalomycins B and C have alternating second sugars attached, α-l-amicetose and α-l-aculose, respectively. The gene cluster for baikalomycins biosynthesis was identified by genome mining, cloned using a transformation-associated recombination technique and successfully expressed in S. albus J1074. It contains a typical set of genes responsible for an angucycline core assembly, all necessary genes for the deoxy sugars biosynthesis, and three genes coding for the glycosyltransferase enzymes. Heterologous expression and deletion experiments allowed to assign the function of glycosyltransferases involved in the decoration of baikalomycins aglycone.

Comparative Genome Analysis and Phenotypic Characterization of Clostridium gasigenes CGAS001 Isolated From Chilled Vacuum-Packed Lamb Meat

“…The antimicrobial activity of the crude polyketide extract was determined by disk diffusion method ( Voitsekhovskaia et al, 2020 ) with modifications. Briefly, the crude extract was suspended in distilled water (0.5 mg/μl) and 50 μl of the mixture loaded on sterile 6 mm disks (Whatman ® , United States).…”

Recently Discovered Secondary Metabolites from Streptomyces Species

“…In a successful attempt to highlight the value of chemical exploration of less investigated ecological niches, Voitsekhovskaia et al isolated anthraquinone derivatives baikalomycins A-C (46-48, Figure 15) from the mollusc (Benedictia baicalensis) endophyte Streptomyces sp. strain IB201691-2A [33]. Baikalomycin A was identified as an aquayamycin derivative modified with β-D-amicetose and two additional hydroxyl groups on C-6a and C-12a of the aglycone.…”

“…Figure 15. The structures of baikalomycins A-C (46-48) and gardenomycins A and B (49 and 50)[33,34].…”

Microbial Secondary Metabolism and Biotechnology

“…As an example, the Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis synthesizes three new angucyclines (baikalomycins A-C), as well as large quantities of rabelomycin and 5-hydroxy-rabelomycin [11]. Baikalomycins A-C exhibited varying levels of anticancer properties.…”