2nd Edition of Pharma R&D and Drug Discovery World Conference 2026

Abstract

Streptomycetes are dominant producers of biologically active secondary metabolites. These soil gram-positive bacteria are characterized by a complex process of morphological differentiation, which is associated with the so-called physiological differentiation, resulting in the production of a considerable number of secondary metabolites with many therapeutic properties (antibiotics, herbicides, antifungal agents, cytostatics, antifungal agents, antiparasitic agents, immunosuppressive agents). S. lavendulae subsp. lavendulae CCM 3239 has been our model organism for studying morphological and physiological differentiation for over 30 years. We have determined the complete genome sequence of this strain. Analysis of the genome sequence led to the identification of 36 biosynthetic gene clusters (BGCs) for various, mostly unknown, secondary metabolites (29 on the genome and 7 on the large linear plasmid pSA3239). One of them, the type II polyketide synthase (PKS) BGC, aur1/aur2, is responsible for the production of aromatic polyktide auricin, which was active against Gram-positive bacteria and showed cytotoxicity against multiple human tumor cell lines. Its biosynthesis is regulated by a complex mechanism through several regulators. Its structural analysis revealed that it has interesting structural features. It is modified with d-forosamine and contains a unique aglycone similar to the griseusin-like spiroketal pyranonaphthoquinones.  The second BGC, bpsA, is responsible for the silent production of blue peptide pigment indigoidine. Genetic manipulation in the BGC for type I PKS induced the production of two new antifungal polyenes. Analysis of the aminoglycoside BGC demonstrated the silent production of streptothricin-like compound active against Gram-negative bacteria. This work was supported by VEGA grant 2/0001/24 from the Slovak Academy of Sciences and the Slovak Research and Development Agency under the contracts No. APVV-24-0023.Streptomycetes are dominant producers of biologically active secondary metabolites. These soil gram-positive bacteria are characterized by a complex process of morphological differentiation, which is associated with the so-called physiological differentiation, resulting in the production of a considerable number of secondary metabolites with many therapeutic properties (antibiotics, herbicides, antifungal agents, cytostatics, antifungal agents, antiparasitic agents, immunosuppressive agents). S. lavendulae subsp. lavendulae CCM 3239 has been our model organism for studying morphological and physiological differentiation for over 30 years. We have determined the complete genome sequence of this strain. Analysis of the genome sequence led to the identification of 36 biosynthetic gene clusters (BGCs) for various, mostly unknown, secondary metabolites (29 on the genome and 7 on the large linear plasmid pSA3239). One of them, the type II polyketide synthase (PKS) BGC, aur1/aur2, is responsible for the production of aromatic polyktide auricin, which was active against Gram-positive bacteria and showed cytotoxicity against multiple human tumor cell lines. Its biosynthesis is regulated by a complex mechanism through several regulators. Its structural analysis revealed that it has interesting structural features. It is modified with d-forosamine and contains a unique aglycone similar to the griseusin-like spiroketal pyranonaphthoquinones.  The second BGC, bpsA, is responsible for the silent production of blue peptide pigment indigoidine. Genetic manipulation in the BGC for type I PKS induced the production of two new antifungal polyenes. Analysis of the aminoglycoside BGC demonstrated the silent production of streptothricin-like compound active against Gram-negative bacteria. This work was supported by VEGA grant 2/0001/24 from the Slovak Academy of Sciences and the Slovak Research and Development Agency under the contracts No. APVV-24-0023.