1.Scale up of a viscous fungal fermentation: application of scale-up criteria with regime analysis and operating boundary conditions.
Pollard DJ1, Kirschner TF, Hunt GR, Tong IT, Stieber R, Salmon PM. Biotechnol Bioeng. 2007 Feb 1;96(2):307-17.
The scale up of the novel, pharmaceutically important pneumocandin (B(0)), from the filamentous fungus Glarea lozoyensis was successfully completed from pilot scale (0.07, 0.8, and 19 m(3)) to production scale (57 m(3)). This was accomplished, despite dissimilar reactor geometry, employing a combination of scale-up criteria, process sensitivity studies, and regime analysis using characteristic time constants for both oxygen mass transfer and bulk mixing. Dissolved oxygen tension, separated from the influence of agitation by gas blending at the 0.07 m(3)-scale, had a marked influence on the concentrations of pneumocandin analogs with different levels of hydroxylation, and these concentrations were used as an indicator of bulk mixing upon scale up. The profound impact of dissolved oxygen tension (DOT) (low and high levels) on analog formation dictated the use of constant DOT, at 80% air saturation, as a scale-up criterion. As a result k(L)a, Oxygen uptake rate (OUR) and hence the OTR were held constant, which were effectively conserved across the scales, while the use of other criterion such as P(g)/V(L), or mixing time were less effective.
2.Genome sequence of the fungus Glarea lozoyensis: the first genome sequence of a species from the Helotiaceae family.
Youssar L1, Grüning BA, Erxleben A, Günther S, Hüttel W. Eukaryot Cell. 2012 Feb;11(2):250. doi: 10.1128/EC.05302-11.
The anamorphic fungus Glarea lozoyensis mutant strain 74030 is an overproducer of pneumocandin B(0), which is chemically converted into Cancidas, a potent antibiotic against clinically important fungal pathogens. Pneumocandins are acylated, cyclic hexapeptides with unusual hydroxylated amino acids. With the Glarea lozoyensis genome, the first species from the large polyphyletic family Helotiaceae has been sequenced.
3.Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis.
Chen L1, Yue Q, Zhang X, Xiang M, Wang C, Li S, Che Y, Ortiz-López FJ, Bills GF, Liu X, An Z. BMC Genomics. 2013 May 20;14:339. doi: 10.1186/1471-2164-14-339.
BACKGROUND: The antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin B0, a lipohexapeptide produced by the fungus Glarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. The nonribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) gene cluster responsible for pneumocandin biosynthesis from G. lozoyensis has not been elucidated to date. In this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of the G. lozoyensis wild-type strain ATCC 20868.
