title: Methanol/sorbitol co-feeding induction enhanced porcine interferon-α production by P. pastoris associated with energy metabolism shift.
abstract: The production of porcine interferon-α (pIFN-α) by Pichia pastoris was largely enhanced when adopting sorbitol/methanol co-feeding induction strategy at 30 °C in a 10-L fermentor. Analysis of energy regeneration pattern and carbon metabolism revealed that major energy metabolism energizing pIFN-α synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle under the methanol/sorbitol co-feeding induction strategy. The sorbitol/methanol co-feeding induction strategy weakened formaldehyde dissimilatory pathway and repressed the accumulation of toxic metabolite-formaldehyde, reduced theoretical oxygen consumption rate and oxygen supply requirement, and increased energy/methanol utilization efficiency so that more methanol could be effectively used for pIFN-α synthesis. As a result, pIFN-α antiviral activity reached a highest level of 1.8 × 10(7) IU/mL which was about 10- to 200-folds of those obtained under pure methanol induction at 20 and 30 °C, respectively.
authors.affiliation: Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People's Republic of China.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Gao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Rui-Song
authors.initials: RS
authors.lastname: Yu
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Wu
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zheng
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Shi
authors.forename: Xiao-Bei
authors.initials: XB
authors.lastname: Zhan
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000818:Animals; D002417:Cattle; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D016898:Interferon-alpha / Q000096:biosynthesis*; D000432:Methanol / Q000378:metabolism*; D010843:Pichia / Q000378:metabolism*; D013012:Sorbitol / Q000378:metabolism*; D013552:Swine
chemical_list: D016898:Interferon-alpha; D013012:Sorbitol; D000432:Methanol