A series of cytostatically active metabolites have been isolated from microorganisms in recent years. These compounds, which are chemically closely related, are of a new structural type. A highly substituted hydrogenated isoindolone unit is fused to an 11-to 14-membered macrocycle. The large ring may be carbocyclic or heterocyclic (lactone or carbonic diester). The absolute configurations of two cytochalasans (phomin and a cytochalasin D derivative) have been established by X-ray analysis. The biogenesis of phomin (cytochalasin B) is broadly known, and it is probable that all cytochalasans have a common biogenetic scheme. All the compounds of this class have a more or less pronounced specifically cytostatic action.
Oxygen supply is a key parameter in aerobic fermentation processes like the industrial production of amino acids. Although the oxygen transfer rate (OTR; or the volumetric oxygen transfer coefficient k(L)a) is routinely analyzed by engineers during stirred tank fermentations, it is often not taken into account by biologists conducting screening experiments in shake flasks. To show the importance of knowing how to avoid oxygen transfer limitations during primary screenings, Corynebacterium glutamicum ATCC 13032 (wild-type strain) and DSM 12866 (lysine-producing strain) were cultivated in shake flasks with different culture liquid volumes and under different shaking conditions. With the Respiration Activity Monitoring System, the OTR was determined quasi-continuously. Optical density as well as concentrations of lysine and byproducts (lactate, acetate, succinate) were determined off-line and correlated with the OTR signal. From the results, design criteria for improved screening in shaken bioreactors that help to avoid selection of suboptimal strains during early process development steps can be derived. Finally, the suitability of DSM 12866 as a strain for industrial processes with a high space-time yield is discussed.
In order to produce sophorolipids from whey, thereby lowering the lactose content and biological oxygen demand, a two-step batch cultivation process was developed including medium sterilization by filtration. In the first step, whey was sterilized by a combination of crossflow and sterile filtration. Because the sophorolipid-producing yeast Candida bombicola ATCC 22214 was not able to use lactose as a carbon source directly, the oleaginous yeast Cryptococcus curvatus ATCC 20509 was grown on deproteinized whey concentrates (DWC). With 1:1 diluted DWC-20, lactose was consumed as the carbon source and biomass (24 g/l dry weight content) as well as single-cell oil (SCO, 10 g/l) were produced. The cultivation broth was disrupted with a glass bead mill and it served as medium for growth (29 g cell dry mass/l) and sophorolipid production (12 g/l) of the yeast C. bombicola.
Herrn Prof. Edgar Ledeyer zum 65. Geburtstag gewidmet (2.5. VI. 73) Szcmmary. Two ncw cytochalasans, proxiphomin and protophomin have been isolated from culturcs of a Phoma species (strain S 298). Thcy are shown t o possess the same skeleton as deoxaphomin (4), which has been isolated recently. Thus they represent lower states of oxidation of 4. On thc basis of the spectral data, the structures 16-methyl-l0-phenyl-[13]cytochalasa-6 (7), 13t, Zlt-triene-l,23-dionc (1) 13t, 19t-trien-l,l7-dion) [5] bewiesen werden. Es ist uns nun gelungen, aus Kulturen der genannten Phoma Species zwei weitere, in geringer Menge gebildete Metabolite zu isolieren, die das gleiche carbocyclische Grundgeriist wie Desoxaphomin (4) besitzen, aber weniger Sauerstoff als dieses enthalten. Im folgenden berichten wir uber die im wesentlichen mit spektroskopischen Methoden durchgefiihrte Strukturaufklarung der beiden neuen Cytochalasane, die wir Proxiphomin und Protophomin nennen, sowie fiber ilire mogliche Funktion im Rahmen der Riogenese der 24-0xa-[14]cytochalasane.
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