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Glycopeptide antibiotics (GPAs) are last defense line drugs against multidrug-resistant Gram-positive pathogens. Natural GPAs teicoplanin and vancomycin, as well as semisynthetic oritavancin, telavancin, and dalbavancin, are currently approved for clinical use. Although these antibiotics remain efficient, emergence of novel GPA-resistant pathogens is a question of time. Therefore, it is important to investigate the natural variety of GPAs coming from so-called “rare” actinobacteria. Herein we describe a novel GPA producer—Nonomuraea coxensisDSM 45129. Its de novosequenced and completely assembled genome harbors a biosynthetic gene cluster (BGC) similar to the dbvBGC of A40926, the natural precursor to dalbavancin. The strain produces a novel GPA, which we propose is an A40926 analogue lacking the carboxyl group on the N-acylglucosamine moiety. This structural difference correlates with the absence of dbv29—coding for an enzyme responsible for the oxidation of the N-acylglucosamine moiety. Introduction of dbv29into N. coxensisled to A40926 production in this strain. Finally, we successfully applied dbv3and dbv4heterologous transcriptional regulators to trigger and improve A50926 production in N. coxensis, making them prospective tools for screening other Nonomuraeaspp. for GPA production. Our work highlights genus Nonomuraeaas a still untapped source of novel GPAs.