title: An integrated control strategy for the fermentation of the marine-derived fungus Aspergillus glaucus for the production of anti-cancer polyketide.
abstract: An integrated control strategy of pH, shear stress, and dissolved oxygen tension (DOT) for fermentation scale-up of the marine-derived fungus Aspergillus glaucus HB 1–19 for the production of the anti-cancer compound aspergiolide A was studied. Keeping initial pH of 6.5 and shifting pH from 6.0 to 7.0 intermittently during the production phase greatly facilitated biosynthesis of aspergiolide A in shake flask cultures. Thus, a pH-shift strategy was proposed that shifting pH to 7.0 once it went lower than 6.0 by pulsed feeding NaOH solution during the production phase in bioreactor fermentation of A. glaucus HB 1–19. As a result, aspergiolide A production in a 30-L bioreactor was increased to 37.6 mg/L, which was 48.6% higher than that in 5-L bioreactor without pH shift. Fermentation scale-up was then performed in a 500-L bioreactor on the basis of an integrated criterion of near-same impeller tip velocity of early phase, DOT levels, and pH shift. The production of aspergiolide A was successfully obtained as 32.0 mg/L, which was well maintained during the process scale-up. This work offers useful information for process development of large-scale production of marine microbial metabolites.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Menghao
authors.initials: M
authors.lastname: Cai
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
authors.forename: Jiushun
authors.initials: J
authors.lastname: Zhou
authors.forename: Chuanpeng
authors.initials: C
authors.lastname: Niu
authors.forename: Li
authors.initials: L
authors.lastname: Kang
authors.forename: Xueqian
authors.initials: X
authors.lastname: Sun
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000880:Anthraquinones / Q000302:isolation & purification / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000378:metabolism*; D059001:Aquatic Organisms / Q000145:classification / Q000378:metabolism*; D001230:Aspergillus / Q000145:classification / Q000378:metabolism*; D061249:Batch Cell Culture Techniques / Q000379:methods*; D019149:Bioreactors / Q000382:microbiology*; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D005285:Fermentation; D009792:Oceans and Seas; D010865:Pilot Projects; D013045:Species Specificity; D018511:Systems Integration
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D003470:Culture Media; C542894:aspergiolide A