Journal Article

Properties, metabolisms, and applications of l-proline analogues

Takagi, Hiroshi, Bach, Thi Mai Hoa

2013

Overview

Due to the unique role of l -proline in the folding and structure of protein, a variety of synthetic proline analogues have been developed. l -Proline analogues have been proven to be valuable reagents for studying cellular metabolism and the regulation of macromolecule synthesis in both prokaryotic and eukaryotic cells. In addition to these fundamental researches, they are useful compounds for industrial use. For instance, microorganisms that overproduce l -proline have been obtained by isolating mutants resistant to l -proline analogues. They are also promising candidates for tuning the biological, pharmaceutical, or physicochemical properties of naturally occurring or de novo designed peptides. Among l -proline analogues, l -azetidine-2-carboxylic acid ( l -AZC) is a toxic non-proteinogenic amino acid originally found in lily of the valley plants and trans -4-hydroxy- l -proline (4- l -THOP) is the most abundant component of mammalian collagen. Many hydroxyprolines (HOPs), such as 4- l -THOP and cis -4-hydroxy- l -proline (4- l -CHOP), are useful chiral building blocks for the organic synthesis of pharmaceuticals. In addition, l -AZC and 4- l -CHOP, which are potent inhibitors of cell growth, have been tested for their antitumor activity in tissue culture and in vivo. In this review, we describe the recent discoveries regarding the physiological properties and microbial production and metabolism of l -proline analogues, particularly l -AZC and HOPs. Their applications in fundamental research and industrial use are also discussed.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: acids / Amino acids / analogs & derivatives / Antibiotics / Azetidinecarboxylic Acid / Biomedical and Life Sciences / Biotechnology / Biotransformation / Carboxylic acids / Cell growth / collagen / Convallaria majalis / drugs / eukaryotic cells / Life Sciences / Metabolism / Microbial Genetics and Genomics / Microbiology / Microorganisms / Mini-Review / mutants / Peptides / Pharmaceuticals / pharmacology / Physicochemical properties / Physiological aspects / Physiology / Polypeptides / Proline / Protein folding / protein structure / Proteins / Reagents / Salinity / Studies / tissue culture / Transfer RNA