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The model system studied involved the cyt\n                      <jats:italic>b<\/jats:italic>\n                      <jats:sub>5<\/jats:sub>\n                      gene being introduced on plasmids into the host with varying copy numbers (0\u20136) under a\n                      <jats:italic>\u03bbP<\/jats:italic>\n                      <jats:sub>L<\/jats:sub>\n                      heat-sensitive promoter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Metabolic profiling involved GC-MS analysis with quality assessments using pooled QCs and multivariate chemometric analysis. This approach revealed specific metabolic features (identified to Level 2 of the Metabolomics Standards Initiative ) correlating significantly with different cultivation conditions and variable copy numbers of the cyt\n                      <jats:italic>b<\/jats:italic>\n                      <jats:sub>5<\/jats:sub>\n                      gene among the examined bacterial strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study shows that CYT\n                      <jats:italic>b<\/jats:italic>\n                      <jats:sub>5<\/jats:sub>\n                      production imposed a substantial energetic burden, reflected by depletion of metabolites associated with the tricarboxylic acid cycle, glycolysis\/gluconeogenesis, pentose phosphate pathway, and glyoxylate metabolism, indicating increased ATP demand. Concurrent reductions in unsaturated fatty acids and changes in lipid-related metabolites suggest membrane remodeling in response to temperature induction (needed to initiate production of CYT\n                      <jats:italic>b<\/jats:italic>\n                      <jats:sub>5<\/jats:sub>\n                      ), as well as metabolic stress. Alterations in glyoxylate shunt and pentose phosphate pathway intermediates further indicate metabolic reprogramming to maintain carbon homeostasis, while significant changes in nucleotide- and amino acid-related metabolites suggest impacts on biosynthetic capacity associated with recombinant expression and gene copy number variation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Overall, these findings demonstrate that CYT\n                      <jats:italic>b<\/jats:italic>\n                      <jats:sub>5<\/jats:sub>\n                      production induces coordinated metabolic adjustments affecting energy-related metabolic pathways, bacterial cell wall and membrane biosynthesis, nucleotide metabolisms and bacterial stress responses, providing valuable insights that may be useful for the optimisation of recombinant protein production processes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-026-02522-5","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:27:34Z","timestamp":1790098054000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic profiling analysis of cytochrome b5 production in E. coli  N4830-1 using GC-MS"],"prefix":"10.1007","volume":"22","author":[{"given":"Thanyaporn","family":"Tengsuttiwat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naheed Nazly","family":"Kaderbhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howbeer","family":"Muhamadali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Royston","family":"Goodacre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"22","key":"2522_CR1","doi-asserted-by":"publisher","first-page":"11928","DOI":"10.1074\/jbc.M115.708149","volume":"291","author":"S Ahn","year":"2016","unstructured":"Ahn, S., Jung, J., Jang, I. 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