title: Selection of objective function in genome scale flux balance analysis for process feed development in antibiotic production.
abstract: Using flux variability analysis of a genome scale metabolic network of Streptomyces coelicolor, a series of reactions were identified, from disparate pathways that could be combined into an actinorhodin-generating mini-network. Candidate process feed nutrients that might be expected to influence this network were used in process simulations and in silico predictions compared to experimental findings. Ranking potential process feeds by flux balance analysis optimisation, using either growth or antibiotic production as objective function, did not correlate with experimental actinorhodin yields in fed processes. However, the effect of the feeds on glucose assimilation rate (using glucose uptake as objective function) ranked them in the same order as in vivo antibiotic production efficiency, consistent with results of a robustness analysis of the effect of glucose assimilation on actinorhodin production.
authors.affiliation: Microbial Science Division, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
authors.forename: Chiraphan
authors.initials: C
authors.lastname: Khannapho
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhao
authors.forename: Bhushan K
authors.initials: BK
authors.lastname: Bonde
authors.forename: Andrzej M
authors.initials: AM
authors.lastname: Kierzek
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Avignone-Rossa
authors.forename: Michael E
authors.initials: ME
authors.lastname: Bushell
mesh_terms: D000880:Anthraquinones / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D004734:Energy Metabolism / Q000502:physiology*; D016680:Genome, Bacterial / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism*; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D005947:Glucose; C013390:actinorhodin; D000095622:Benzoisochromanequinones