The growing resistance of microorganisms towards antibiotics has become a serious global problem. Therapeutics with novel chemical scaffolds and/or mechanisms of action are urgently needed to combat infections caused by multidrug resistant pathogens, including bacteria, fungi and viruses. Development of novel antimicrobial agents is still highly dependent on the discovery of new natural products. At present, most antimicrobial drugs used in medicine are of natural origin. Among the natural producers of bioactive substances, Actinobacteria continue to be an important source of novel secondary metabolites for drug application. In this review, the authors report on the bioactive antimicrobial secondary metabolites of Actinobacteria that were described between 2011 and April 2018. Special attention is paid to the chemical scaffolds, biological activities and origin of these novel antibacterial, antifungal and antiviral compounds. Arenimycin C, chromopeptide lactone RSP 01, kocurin, macrolactins A1 and B1, chaxamycin D as well as anthracimycin are regarded as the most effective compounds with antibacterial activity. In turn, the highest potency among selected antifungal compounds is exhibited by enduspeptide B, neomaclafungins A-I and kribelloside D, while ahmpatinin i Bu, antimycin A1a, and pentapeptide 4862F are recognized as the strongest antiviral agents.

A new metabolite, cyclic dipeptide, cis-(3S,8aS)-3-(3,4-dihydroxybenzyl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, named JS-3 was isolated from Streptomyces sp. 8812 fermentation broth. Its chemical structure was established by means of spectroscopic analysis. A wide-range-screening study, which included inhibition assay of DD-carboxypeptidase/transpeptidase activity, determination of antibacterial, antifungal, and antiproliferative activities as well as free-radical scavenging was performed. To authors knowledge, this is the first isolation of such compound from natural sources and the first one from bacteria, Streptomyces.

Aim of the study  Isolation and purification of a new metabolite fromStreptomyces badius ATCC19888 fermentation broth. Determination of chemical structure of isolated compound. Evaluation of its biological activities. Materials and MethodsStrain: Streptomyces badius ATCC 19888 was isolated from the soil in Kaukasus (Russia).Fermentation and purification: fermenter (Sartorius Biostat A, Germany), HPLC (Knauer). NMR analysis:The 1D 1 H and 13C NMR spectra as well as 2D homo-and heteronuclear spectra were collected on a 700MHz Bruker AVANCE III spectrometer, equipped with a QCI CryoProbe Experiments were performed at 25°C. Spectra were processed and prepared with TopSpin 3.0 Bruker Software. HR MS analysis: MaldiSYNAPT G2-S HDMS (Waters) coupled with ACQUITY UPLC I-Class System (Waters).