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Biomolecular Concepts

Editor-in-Chief: Di Cera, Enrico


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Volume 4, Issue 2

Issues

Transport of substrates into peroxisomes: the paradigm of β-lactam biosynthetic intermediates

Juan-Francisco Martín
  • Corresponding author
  • Area of Microbiology, Department of Molecular Biology, University of Leon, E-24071 León, Spain
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Carlos García-Estrada
  • INBIOTEC, Institute of Biotechnology of Leon, Avenida Real no. 1, Parque Científico de León, E-24006 León, Spain
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ricardo V. Ullán
  • INBIOTEC, Institute of Biotechnology of Leon, Avenida Real no. 1, Parque Científico de León, E-24006 León, Spain
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-02-06 | DOI: https://doi.org/10.1515/bmc-2012-0048

Abstract

Peroxisomes are ubiquitous organelles that enclose catalases, fatty acid-oxidizing enzymes, and a variety of proteins involved in different cellular processes. Interestingly, the late enzymes involved in penicillin biosynthesis, and the isopenicillin N epimerization enzymes involved in cephalosporin biosynthesis are located inside peroxisomes in the producer fungi Penicillium chrysogenum and Acremonium chrysogenum. Peroxisome proteins are targeted to those organelles by peroxisomal targeting signals located at the C-terminus (PTS1) or near the N-terminal end (PTS2) of those proteins. Peroxisomal membrane proteins (PMPs) are largely recruited by the interaction with specific sequences in the Pex19 protein. The compartmentalization into peroxisomes of several steps of the biosynthesis of penicillin, cephalosporin, and other secondary metabolites raises the question of how the precursors and/or intermediates of the biosynthesis of β-lactam antibiotics are transported into peroxisomes and the mechanisms of secretion of the final products (penicillin or cephalosporin) from peroxisomes to the extracellular medium. Recent advances in peroxisome proteomics, immunoelectron microscopy, and fluorescence labeling have shown that the transport of these intermediates is mediated by membrane proteins of the major facilitator superfamily class (drug/H+ antiporters) containing 12 transmembrane-spanning domains (TMS). In some cases, the transport of the substrates (e.g., fatty acids) or intermediates may be mediated by ATP-binding cassette (ABC) transporters. Knowledge on the transport and secretion mechanisms is of paramount importance to understand the complex mechanisms of cell differentiation and their crosstalk with the biosynthesis of different secondary metabolites that act as biochemical signals between the producer cells and also as communication signals with competing microorganisms (e.g., antimicrobial agents or plant elicitors).

Keywords: β-lactams; biosynthesis enzymes; drug/H+ antiporters; major facilitator superfamily; peroxisomes; transport of intermediates

About the article

Juan-Francisco Martín

Dr. Juan F. Martín is Professor of Microbiology at the University of León (Spain). He graduated in Chemistry and did his PhD thesis on fungal microbial biochemistry at the University of Salamanca (Spain) in 1971. He was a postdoctoral researcher at the Waksman Institute of Microbiology (1971–1974) Rutgers University, New Jersey (USA) and in 1974 moved to the M.I.T. (Department of Food Science) at Boston, Mass (USA) working with Prof. Arnold L. Demain. After returning to Spain with a tenure position at the Spanish Research Council (CSIC) he got a position as Professor at the University of Salamanca and in 1980 a Professor tenure at the University of León. He founded in 1991 the Institute of Biotechnology of León (INBIOTEC) and directed it until 2011. His field of expertise is centered in microbial genetics and biochemistry, particularly in fungi, Streptomyces and Corynebacteria. He is author of 460 scientific publications and review articles and serves as member of the editorial board of several scientific journals. In 1999 was awarded with the ARIMA prize by the IUMS.

Carlos García-Estrada

Carlos García-Estrada received his Bachelor degree in Veterinary Sciences from the University of León (Spain, 1998) and obtained his DPhil from the same University in 2003. During this period, he completed his professional training at the National Center for Natural Products Research, University of Mississippi, MS, USA (2002). Subsequently he started his postdoctoral studies under the supervision of Professor Juan-Francisco Martín at the Institute of Biotechnology (INBIOTEC), León, Spain, where he worked with fungal secondary metabolism. He completed his postdoctoral stage at the Department of Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands (2005). Currently, he is the Head of the Biopharma and Biomedicine Area at INBIOTEC and combines this activity with a position as associate professor at the University of León (Spain). His research interests center on the biosynthesis of antibiotics and other secondary metabolites by fungi.

Ricardo V. Ullán

Ricardo Vicente Ullán received his Bachelor degree in Biology Sciences from the University of Salamanca (Spain, 1995) and obtained his PhD from the University of León in 2002. He started his postdoctoral studies under the supervision of Professor Juan-Francisco Martín at the University of León, Spain, where he worked on the biosynthesis of secondary metabolites by fungi. He completed his postdoctoral stage at the Universities of Manchester (United Kingdom) and Santiago de Compostela (Spain). Currently, he is the Head of the Environmental Area at the Institute of Biotechnology (INBIOTEC) and Associate Professor at the University of León (Spain). His research interests are focused on the Environmental Biotechnology.


Corresponding author: Juan-Francisco Martín, Area of Microbiology, Department of Molecular Biology, University of Leon, E-24071 León, Spain


Received: 2012-11-09

Accepted: 2012-12-21

Published Online: 2013-02-06

Published in Print: 2013-04-01


Citation Information: BioMolecular Concepts, Volume 4, Issue 2, Pages 197–211, ISSN (Online) 1868-503X, ISSN (Print) 1868-5021, DOI: https://doi.org/10.1515/bmc-2012-0048.

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Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2016, Volume 1863, Number 5, Page 838
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M. Fernández-Aguado, J.F. Martín, R. Rodríguez-Castro, C. García-Estrada, S.M. Albillos, F. Teijeira, and R.V. Ullán
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Pedro I. Hidalgo, Ricardo V. Ullán, Silvia M. Albillos, Olimpio Montero, María Ángeles Fernández-Bodega, Carlos García-Estrada, Marta Fernández-Aguado, and Juan-Francisco Martín
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Carlos García-Estrada, Carlos Barreiro, Mohammad-Saeid Jami, Jorge Martín-González, and Juan-Francisco Martín
Journal of Proteomics, 2013, Volume 85, Page 129

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