Old and new glycopeptide antibiotics: From product to gene and back in the post-genomic era

Giorgia Letizia Marcone; Elisa Binda; Francesca Berini; Flavia Marinelli

doi:10.1016/j.biotechadv.2018.02.009

Old and new glycopeptide antibiotics: From product to gene and back in the post-genomic era

Biotechnol Adv. 2018 Mar-Apr;36(2):534-554. doi: 10.1016/j.biotechadv.2018.02.009. Epub 2018 Feb 15.

Authors

Giorgia Letizia Marcone¹, Elisa Binda², Francesca Berini³, Flavia Marinelli⁴

Affiliations

¹ Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy; The Protein Factory Research Center, Politecnico di Milano and University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy. Electronic address: giorgia.marcone@uninsubria.it.
² Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy; The Protein Factory Research Center, Politecnico di Milano and University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy. Electronic address: elisa.binda@uninsubria.it.
³ Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy; The Protein Factory Research Center, Politecnico di Milano and University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy. Electronic address: f.berini@uninsubria.it.
⁴ Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy; The Protein Factory Research Center, Politecnico di Milano and University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy. Electronic address: flavia.marinelli@uninsubria.it.

PMID: 29454983
DOI: 10.1016/j.biotechadv.2018.02.009

Abstract

Glycopeptide antibiotics are drugs of last resort for treating severe infections caused by multi-drug resistant Gram-positive pathogens. First-generation glycopeptides (vancomycin and teicoplanin) are produced by soil-dwelling actinomycetes. Second-generation glycopeptides (dalbavancin, oritavancin, and telavancin) are semi-synthetic derivatives of the progenitor natural products. Herein, we cover past and present biotechnological approaches for searching for and producing old and new glycopeptide antibiotics. We review the strategies adopted to increase microbial production (from classical strain improvement to rational genetic engineering), and the recent progress in genome mining, chemoenzymatic derivatization, and combinatorial biosynthesis for expanding glycopeptide chemical diversity and tackling the never-ceasing evolution of antibiotic resistance.

Keywords: A40926; Combinatorial biochemistry; Dalbavancin; Fermentation; Genetic engineering; Glycopeptide antibiotics; Natural product screening; Strain improvement; Teicoplanin; Vancomycin.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Anti-Bacterial Agents*
Biotechnology
Drug Discovery
Genetic Engineering
Genomics
Lipoglycopeptides*

Substances

Anti-Bacterial Agents
Lipoglycopeptides