Abstract
Despite oxygen is believed to be the most important environmental factor for any aerobic microbial process, the quantitative studies of its influence on growth and metabolite formation on the level of individual pellets formed by filamentous fungi were seldom performed. Never was it made for lovastatin producer Aspergillus terreus ATCC20542. Thus, this work is a quantitative study of oxygen transfer into A. terreus pellets during lovastatin biosynthesis in the shake flask culture. The basic measurement tool was an oxygen microprobe allowing for obtaining oxygen concentration profiles in the pellets. The pellets of various sizes from 1,600 to 6,400 μm exerting different oxygen transfer conditions were studied. Also various initial concentrations of carbon source were applied to change the conditions of biological reaction running in the pellets. Effective diffusivities in A. terreus pellets ranged from 643 to 1,342 μm s−1 dependent on their size and structure. It occurred that only the smallest pellets of diameter equal to about 1,400 μm were fully penetrated by oxygen. What is more, apart from the size of pellets, the appropriate lactose concentration was required to effectively produce lovastatin. Its value was correlated with oxygen concentration on the surface of the pellet and could not be either too high, as the aforementioned oxygen level tended then to zero, or too low, as despite high oxygen concentration no biological reaction ran in the pellet and no lovastatin was formed.
Highlights
Lovastatin is a polyketide secondary metabolite from Aspergillus terreus
This work is a quantitative study of oxygen transfer into A. terreus pellets during lovastatin biosynthesis in the shake flask culture
Its value was correlated with oxygen concentration on the surface of the pellet and could not be either too high, as the aforementioned oxygen level tended to zero, or too low, as despite high oxygen concentration no biological reaction ran in the pellet and no lovastatin was formed
Summary
Lovastatin is a polyketide secondary metabolite from Aspergillus terreus. It plays an important role in medicine being a competitive inhibitor of S-3-hydroxymethylglutaryl-CoA reductase and decreasing in this way the level of endogenous cholesterol in human organisms.As lovastatin is produced by filamentous fungi, i.e. strictly aerobic organisms, its formation is affected by oxygen saturation in the cultivation broth [1]. Lovastatin is a polyketide secondary metabolite from Aspergillus terreus. It plays an important role in medicine being a competitive inhibitor of S-3-hydroxymethylglutaryl-CoA reductase and decreasing in this way the level of endogenous cholesterol in human organisms. The formation of pellets of various sizes by A. terreus in the submerged culture and the fact that fungal suspensions may have changeable rheological properties during the cultivation make oxygen transfer processes one of the most important issues to be studied for the efficient lovastatin formation. The importance of oxygen for lovastatin formation made several researchers aerate their pelleted cultures even with oxygen-enriched air [2, 3, 8]. Bizukojc and Ledakowicz [9] and Lai et al [1, 10] claimed that too much oxygen was not favourable for lovastatin formation
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