Artigo Revisado por pares

Dynamic flux balance analysis for pharmaceutical protein production by Pichia pastoris: Human growth hormone

2010; Elsevier BV; Volume: 48; Issue: 3 Linguagem: Inglês

10.1016/j.enzmictec.2010.09.016

ISSN

1879-0909

Autores

Pınar Çalı́k, Merve Şahin, Hatice Taşpınar, Elif Ş. Soyaslan, Bahar İnankur,

Tópico(s)

Protein purification and stability

Resumo

The influence of methanol feeding rate on intracellular reaction network of recombinant human growth hormone (rhGH) producing Pichia pastoris was investigated at three different specific growth rates, namely, 0.02 (MS-0.02), 0.03 (MS-0.03), and 0.04 h(-1) (MS-0.04) where Period-I (33 ≤ t <42 h) includes the early exponential growth phase; Period-II (42 ≤ t 51 h) is the diminution phase for rhGH and cell synthesis. In Period-I, almost all of the formaldehyde entered the assimilatory pathway, at MS-0.02 and MS-0.03, whereas, at MS-0.04 high methanol feeding rate resulted in an adaptation problem. In Period-III, only at MS-0.02 co-carbon source sorbitol uptake-flux was active showing that sorbitol uptake does not affected from the predetermined feeding rate of methanol at μ(0)>0.02 h(-1). The biomass synthesis flux value was the highest in Period-I, -II and -III, respectively at MS-0.03 & MS-0.04, MS-0.04 and MS-0.02; whereas, rhGH flux was the highest in Period-I, -II, and -III, respectively at MS-0.03, MS-0.02 and MS-0.03. Based on the fluxes, Period-I should start with MS-0.03 methanol feeding rate and starting from the middle of Period-II methanol feeding rate should be shifted to MS-0.02.

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