title: Optimization of rifamycin B fermentation in shake flasks via a machine-learning-based approach.
abstract: Rifamycin B is an important polyketide antibiotic used in the treatment of tuberculosis and leprosy. We present results on medium optimization for Rifamycin B production via a barbital insensitive mutant strain of Amycolatopsis mediterranei S699. Machine-learning approaches such as Genetic algorithm (GA), Neighborhood analysis (NA) and Decision Tree technique (DT) were explored for optimizing the medium composition. Genetic algorithm was applied as a global search algorithm while NA was used for a guided local search and to develop medium predictors. The fermentation medium for Rifamycin B consisted of nine components. A large number of distinct medium compositions are possible by variation of concentration of each component. This presents a large combinatorial search space. Optimization was achieved within five generations via GA as well as NA. These five generations consisted of 178 shake-flask experiments, which is a small fraction of the search space. We detected multiple optima in the form of 11 distinct medium combinations. These medium combinations provided over 600% improvement in Rifamycin B productivity. Genetic algorithm performed better in optimizing fermentation medium as compared to NA. The Decision Tree technique revealed the media-media interactions qualitatively in the form of sets of rules for medium composition that give high as well as low productivity.
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology, Bombay, Powai, Mumbai 400 076, India.
authors.forename: Prashant M
authors.initials: PM
authors.lastname: Bapat
authors.forename: Pramod P
authors.initials: PP
authors.lastname: Wangikar
mesh_terms: D000192:Actinomycetales / Q000378:metabolism*; D000465:Algorithms; D001185:Artificial Intelligence; D019149:Bioreactors / Q000382:microbiology*; D018929:Cell Culture Techniques / Q000379:methods*; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism; D003661:Decision Support Techniques; D005285:Fermentation / Q000502:physiology; D008954:Models, Biological; D012294:Rifamycins / Q000096:biosynthesis*
chemical_list: D003470:Culture Media; D012294:Rifamycins; C033974:rifamycin B