Secondary Metabolites From Streptomyces Spp. CPCC 200267 And CPCC 204293

Actinomycetes produce a diverse range of metabolites with complex structures,and have been known as a significant source of lead compounds in drug discovery for a long time.Literatures indicate that 70%of known antibiotics are derived from actinomycetes.Among actinomycetes,Streptomyces is the dominant genus,and can produce the largest number and variety of antibiotics.Streptomyces is widely distributed in soil,marine environments,extreme environments and organisms.However,a large amount of published Streptomyces genome information reveal that the number of secondary metabolite biosynthetic gene clusters in Streptomyces far exceeds the total number of reported secondary metabolites,and a large number of biosynthetic gene clusters are silent,which suggests that Streptomyces has remarkable biosynthetic potential that has yet to be fully harnessed.Based on the rich microbial resources of the China Pharmaceutical Culture Collection Center,we carry out a large number of preliminary biological activity screening and preliminary secondary metabolites analysis.Two strains CPCC 200267 and CPCC 204293 from Streptomyces were ultimately selected for the isolation and structural identification of secondary metabolites.Initially,metabolite analysis was conducted on Streptomyces sp.CPCC 200267,which revealed geninthiocins as its main metabolites.Subsequently,the culture conditions were optimized using the OSMAC strategy.Various methods,such as altering the culture medium components and adding enzyme inhibitors,were applied to enhance geninthiocins expression and further enrich its metabolic capacity.Large-scale fermentation was then carried out,and the metabolites were isolated and purified using various methods such as extraction,normal phase silica gel column chromatography,reversed phase silica gel column chromatography,Sephadex LH-20 column chromatography,and semi-preparative HPLC.Six geninthiocin derivatives(1-6)including two new compounds(1 and 2)were obtained.The six compounds were identified as geninthiocin E(1),geninthiocin F(2),val-geninthiocin(3),geninthiocin A(4),geninthiocin B(5),and geninthiocin C(6).For Streptomyces sp.CPCC 204293,the main product was identified as a 28membered macrocyclic lactone,and the OSMAC strategy was used to optimize the culture conditions.Large-scale fermentation was conducted,and the compounds were isolated and purified by extraction,normal-phase silica gel column chromatography,reversed-phase silica gel column chromatography,Sephadex LH-20 column chromatography,and semi-preparative HPLC,followed by structure identification using modern spectroscopic techniques such as IR,UV,and NMR.A total of eight 28membered macrocyclic lactone derivatives(7-14)were obtained,among which compounds 7-9 were new compounds.The eight compounds were identified as strekatramycin A(7),strekatramycin B(8),strekatramycin C(9),AB023a(10),AB023b(11),takanawaene A(12),takanawaene B(13),and takanawaene C(14).Finally,the compounds 1-6 were subjected to evaluate for antibacterial and antiviral activits.The results revealed that compounds 1,3,4,and 5 exhibited good inhibitory effects on influenza A virus,with IC50 values of 28.71,15.34,7.26,and 18.25 μM,respectively.Moreover,compounds 3 and 4 displayed inhibitory effects on Staphylococcus aureus ATCC 29213.The activity testing for compounds 7-14 remains to be carried out.