Gaspari, ErikaMalachowski, AntoniGarcía Morales, LuisBurgos, RaulSerrano Pubull, Luis, 1982-Martins dos Santos, VitorSuarez-Diez, Maria2020-11-162020-11-162020Gaspari E, Malachowski A, Garcia-Morales L, Burgos R, Serrano L, Martins Dos Santos VAP, Suarez-Diez M. Model-driven design allows growth of Mycoplasma pneumoniae on serum-free media. NPJ Syst Biol Appl. 2020; 6(1):33. DOI: 10.1038/s41540-020-00153-72056-7189http://hdl.handle.net/10230/45770Mycoplasma pneumoniae is a slow-growing, human pathogen that causes atypical pneumonia. Because it lacks a cell wall, many antibiotics are ineffective. Due to its reduced genome and dearth of many biosynthetic pathways, this fastidious bacterium depends on rich, undefined medium for growth, which makes large-scale cultivation challenging and expensive. To understand factors limiting growth, we developed a genome-scale, constraint-based model of M. pneumoniae called iEG158_mpn to describe the metabolic potential of this bacterium. We have put special emphasis on cell membrane formation to identify key lipid components to maximize bacterial growth. We have used this knowledge to predict essential components validated with in vitro serum-free media able to sustain growth. Our findings also show that glycolysis and lipid metabolism are much less efficient under hypoxia; these findings suggest that factors other than metabolism and membrane formation alone affect the growth of M. pneumoniae. Altogether, our modelling approach allowed us to optimize medium composition, enabled growth in defined media and streamlined operational requirements, thereby providing the basis for stable, reproducible and less expensive production.application/pdfeng© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41540-020-00153-7Biochemical networksComputational biology and bioinformaticsComputer modellingMetabolic engineeringinfo:eu-repo/semantics/openAccess