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Regulation and compartmentalization of β‐lactam biosynthesis

Penicillins and cephalosporins are β‐lactam antibiotics widely used in human medicine. The biosynthesis of these compounds starts by the condensation of the amino acids l‐α‐aminoadipic acid, l‐cysteine and l‐valine to form the tripeptide δ‐l‐α‐aminoadipyl‐l‐cysteinyl‐d‐valine catalysed by the non‐ri...

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Autores principales: Martín, Juan F., Ullán, Ricardo V., García‐Estrada, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815371/
https://www.ncbi.nlm.nih.gov/pubmed/21255328
http://dx.doi.org/10.1111/j.1751-7915.2009.00123.x
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author Martín, Juan F.
Ullán, Ricardo V.
García‐Estrada, Carlos
author_facet Martín, Juan F.
Ullán, Ricardo V.
García‐Estrada, Carlos
author_sort Martín, Juan F.
collection PubMed
description Penicillins and cephalosporins are β‐lactam antibiotics widely used in human medicine. The biosynthesis of these compounds starts by the condensation of the amino acids l‐α‐aminoadipic acid, l‐cysteine and l‐valine to form the tripeptide δ‐l‐α‐aminoadipyl‐l‐cysteinyl‐d‐valine catalysed by the non‐ribosomal peptide ‘ACV synthetase’. Subsequently, this tripeptide is cyclized to isopenicillin N that in Penicillium is converted to hydrophobic penicillins, e.g. benzylpenicillin. In Acremonium and in streptomycetes, isopenicillin N is later isomerized to penicillin N and finally converted to cephalosporin. Expression of genes of the penicillin (pcbAB, pcbC, pendDE) and cephalosporin clusters (pcbAB, pcbC, cefD1, cefD2, cefEF, cefG) is controlled by pleitropic regulators including LaeA, a methylase involved in heterochromatin rearrangement. The enzymes catalysing the last two steps of penicillin biosynthesis (phenylacetyl‐CoA ligase and isopenicillin N acyltransferase) are located in microbodies, as shown by immunoelectron microscopy and microbodies proteome analyses. Similarly, the Acremonium two‐component CefD1–CefD2 epimerization system is also located in microbodies. This compartmentalization implies intracellular transport of isopenicillin N (in the penicillin pathway) or isopenicillin N and penicillin N in the cephalosporin route. Two transporters of the MFS family cefT and cefM are involved in transport of intermediates and/or secretion of cephalosporins. However, there is no known transporter of benzylpenicillin despite its large production in industrial strains.
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spelling pubmed-38153712014-02-12 Regulation and compartmentalization of β‐lactam biosynthesis Martín, Juan F. Ullán, Ricardo V. García‐Estrada, Carlos Microb Biotechnol Minireviews Penicillins and cephalosporins are β‐lactam antibiotics widely used in human medicine. The biosynthesis of these compounds starts by the condensation of the amino acids l‐α‐aminoadipic acid, l‐cysteine and l‐valine to form the tripeptide δ‐l‐α‐aminoadipyl‐l‐cysteinyl‐d‐valine catalysed by the non‐ribosomal peptide ‘ACV synthetase’. Subsequently, this tripeptide is cyclized to isopenicillin N that in Penicillium is converted to hydrophobic penicillins, e.g. benzylpenicillin. In Acremonium and in streptomycetes, isopenicillin N is later isomerized to penicillin N and finally converted to cephalosporin. Expression of genes of the penicillin (pcbAB, pcbC, pendDE) and cephalosporin clusters (pcbAB, pcbC, cefD1, cefD2, cefEF, cefG) is controlled by pleitropic regulators including LaeA, a methylase involved in heterochromatin rearrangement. The enzymes catalysing the last two steps of penicillin biosynthesis (phenylacetyl‐CoA ligase and isopenicillin N acyltransferase) are located in microbodies, as shown by immunoelectron microscopy and microbodies proteome analyses. Similarly, the Acremonium two‐component CefD1–CefD2 epimerization system is also located in microbodies. This compartmentalization implies intracellular transport of isopenicillin N (in the penicillin pathway) or isopenicillin N and penicillin N in the cephalosporin route. Two transporters of the MFS family cefT and cefM are involved in transport of intermediates and/or secretion of cephalosporins. However, there is no known transporter of benzylpenicillin despite its large production in industrial strains. Blackwell Publishing Ltd 2010-05 2010-04-20 /pmc/articles/PMC3815371/ /pubmed/21255328 http://dx.doi.org/10.1111/j.1751-7915.2009.00123.x Text en Copyright© 2009 The Authors. Journal compilation © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd
spellingShingle Minireviews
Martín, Juan F.
Ullán, Ricardo V.
García‐Estrada, Carlos
Regulation and compartmentalization of β‐lactam biosynthesis
title Regulation and compartmentalization of β‐lactam biosynthesis
title_full Regulation and compartmentalization of β‐lactam biosynthesis
title_fullStr Regulation and compartmentalization of β‐lactam biosynthesis
title_full_unstemmed Regulation and compartmentalization of β‐lactam biosynthesis
title_short Regulation and compartmentalization of β‐lactam biosynthesis
title_sort regulation and compartmentalization of β‐lactam biosynthesis
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815371/
https://www.ncbi.nlm.nih.gov/pubmed/21255328
http://dx.doi.org/10.1111/j.1751-7915.2009.00123.x
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