Comparative genomics revealed key molecular targets to rapidly convert a reference rifamycin-producing bacterial strain into an overproducer by genetic engineering
Abstract
Rifamycins are mainstay agents in treatment of many widespread diseases, but how an improved rifamycin producer can be created is still incompletely understood. Here, we describe a comparative genomic approach to investigate the mutational patterns introduced by the classical mutate-and-screen method in the genome of an improved rifamycin producer. Comparing the genome of the rifamycin B overproducer Amycolatopsis mediterranei HP-130 with those of the reference strains A. mediterranei S699 and U32, we identified 250 variations, affecting 227 coding sequences (CDS), 109 of which were HP-130-specific since they were absent in both S699 and U32. Mutational and transcriptional patterns indicated a series of genomic manipulations that not only proved the causative effect of mutB2 (coding for methylmalonyl-CoA mutase large subunit) and argS2 (coding for arginyl tRNA synthetase) mutations on the overproduction of rifamycin, but also constituted a rational strategy to genetically engineer a reference strain into an overproducer.
Tutti gli autori
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Peano C. , Damiano F. , Forcato M. , Pietrelli A. , Palumbo C. , Corti G. , Siculella L. , Fuligni F. , Tagliazucchi G.M. , De Benedetto G.E. , Bicciato S. , De Bellis G. , Alifano P.
Titolo volume/Rivista
METABOLIC ENGINEERING
Anno di pubblicazione
2014
ISSN
1096-7176
ISBN
Non Disponibile
Numero di citazioni Wos
7
Ultimo Aggiornamento Citazioni
28/04/2018
Numero di citazioni Scopus
9
Ultimo Aggiornamento Citazioni
28/04/2018
Settori ERC
Non Disponibile
Codici ASJC
Non Disponibile
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