caa a22 4500 605503168 CHVBK 20210128100609.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00253-015-6531-3 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6531-3 Enhanced C30 carotenoid production in Bacillus subtilis by systematic overexpression of MEP pathway genes [Elektronische Daten] [Dan Xue, Ingy Abdallah, Ilse de Haan, Mark Sibbald, Wim Quax] Creating novel biosynthetic pathways and modulating the synthesis of important compounds are one of the hallmarks of synthetic biology. Understanding the key parameters controlling the flux of chemicals throughout a metabolic pathway is one of the challenges ahead. Isoprenoids are the most functionally and structurally diverse group of natural products from which numerous medicines and relevant fine chemicals are derived. The well-characterized and broadly used production organism Bacillus subtilis forms an ideal background for creating and studying novel synthetic routes. In comparison to other bacteria, B. subtilis emits the volatile compound isoprene, the smallest representative of isoprenoids, in high concentrations and thus represents an interesting starting point for an isoprenoid cell factory. In this study, the effect of systematic overexpression of the genes involved in the methylerythritol phosphate (MEP) pathway on isoprenoid production in B. subtilis was investigated. B. subtilis strains harboring a plasmid containing C30 carotenoid synthetic genes, crtM and crtN, were combined with pHCMC04G plasmids carrying various synthetic operons of the MEP pathway genes. The levels of produced carotenoids, diaponeurosporene and diapolycopene, were used as indication of the role of the various enzymes on the flux of the MEP pathway. It was shown that the production of carotenoids can be increased significantly by overexpressing the MEP pathway enzymes. More broadly, the strains developed in this study can be used as a starting point for various isoprenoid cell factories. The Author(s), 2015 Terpenoids nationallicence MEP nationallicence Bacillus subtilis nationallicence Isoprene nationallicence Carotenoid nationallicence Xue Dan Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut Abdallah Ingy Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut de Haan Ilse Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut Sibbald Mark Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut Quax Wim Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/14(2015-07-01), 5907-5915 0175-7598 99:14<5907 2015 99 253 https://doi.org/10.1007/s00253-015-6531-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6531-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Xue Dan Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Abdallah Ingy Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut NATIONALLICENCE 700 1- de Haan Ilse Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Sibbald Mark Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Quax Wim Department of Pharmaceutical Biology, GRIP, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/14(2015-07-01), 5907-5915 0175-7598 99:14<5907 2015 99 253