Understanding the Glycopeptide Antibiotic Crosslinking Cascade: In Vitro Approaches Reveal the Details of a Complex Biosynthesis Pathway.

Chembiochem : a European Journal of Chemical Biology
Yongwei ZhaoMax J Cryle

Abstract

The glycopeptide antibiotics (GPAs) are a fascinating example of complex natural product biosynthesis, with the nonribosomal synthesis of the peptide core coupled to a cytochrome P450-mediated cyclisation cascade that crosslinks aromatic side chains within this peptide. Given that the challenges associated with the synthesis of GPAs stems from their highly crosslinked structure, there is great interest in understanding how biosynthesis accomplishes this challenging set of transformations. In this regard, the use of in vitro experiments has delivered important insights into this process, including the identification of the unique role of the X-domain as a platform for P450 recruitment. In this minireview, we present an analysis of the results of in vitro studies into the GPA cyclisation cascade that have demonstrated both the tolerances and limitations of this process for modified substrates, and in turn developed rules for the future reengineering of this important antibiotic class.

References

Jan 2, 2004·Microbiology·Margherita SosioStefano Donadio
May 13, 2004·Journal of the American Chemical Society·Stefan WeistRoderich D Süssmuth
May 30, 2006·Journal of Biotechnology·Evi StegmannWolfgang Wohlleben
May 18, 2007·BMC Evolutionary Biology·Christian RauschDaniel H Huson
Dec 11, 2007·Bioorganic & Medicinal Chemistry Letters·Nina GeibJohn A Robinson
Aug 9, 2008·Organic & Biomolecular Chemistry·Katharina WoitheJohn A Robinson
Oct 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Max J Cryle, Ilme Schlichting
Nov 6, 2008·Protein Expression and Purification·Julius BogomolovasGunter Stier
Oct 6, 2010·Current Opinion in Microbiology·Evi StegmannWolfgang Wohlleben
Oct 27, 2010·Archives of Biochemistry and Biophysics·Max J CryleIlme Schlichting
Jan 19, 2011·Metallomics : Integrated Biometal Science·Max J Cryle
Jul 25, 2013·Bioorganic & Medicinal Chemistry Letters·Joseph R Pinchman, Dale L Boger
Nov 14, 2013·The Journal of Antibiotics·Grace YimGerard Wright
Apr 24, 2014·Organic & Biomolecular Chemistry·Patrick C SchmartzJohn A Robinson
Nov 2, 2014·Chembiochem : a European Journal of Chemical Biology·Kristina HaslingerMax J Cryle
May 6, 2015·Natural Product Reports·Rashed S Al TomaRoderich D Süssmuth
May 24, 2016·Journal of the American Chemical Society·Madeleine PeschkeMax J Cryle
Oct 19, 2016·Scientific Reports·Madeleine PeschkeMax J Cryle
Mar 23, 2017·Angewandte Chemie·Roderich D Süssmuth, Andi Mainz
Apr 25, 2017·Chemical Reviews·Akinori OkanoDale L Boger

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.