Antibiotics 2018, 7(2), 30; https://doi.org/10.3390/antibiotics7020030
Complex Regulatory Networks Governing Production of the Glycopeptide A40926
1
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Università degli Studi di Palermo, Viale delle Scienze Bd.16, 90128 Palermo, Italy
2
Via Ortles 22/4, Naicons Srl, 20139 Milano, Italy
3
Via Ortles 22/4, Ktedogen Srl, 20139 Milano, Italy
*
Author to whom correspondence should be addressed.
Received: 9 March 2018 / Revised: 29 March 2018 / Accepted: 3 April 2018 / Published: 5 April 2018
(This article belongs to the Special Issue Actinomycetes: The Antibiotics Producers)
Abstract
Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis. This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoBR, have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain. View Full-TextKeywords:
glycopeptide antibiotics; dbv cluster; regulatory genes; StrR; LAL; LuxR solo; dalbavancin; A40926
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Alduina, R.; Sosio, M.; Donadio, S. Complex Regulatory Networks Governing Production of the Glycopeptide A40926. Antibiotics 2018, 7, 30.
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