Microbial process translation--laboratory to pilot plant at the Frederick Cancer Research Center.

In summary, operations in the FCRC pilot plant have included training an operating staff, operability trials, equipment modification and repair, and supplementation of the original equipment to gain greater versatility. In addition to effort spent on proving and improving the capacity of the pilot plant, development studies and production operations involving translation of laboratory operations to pilot level or volume have included: 1. Development of a production process for interferon as described above. As a by-product of the interferon program, samples of cell culture have been studied in the Basic Research Division of FCRC for the production of lymphokines. 2. Production of starting materials (cell paste) for carboxypeptidase G1, using three different organisms, and production of refined material from the FCRC 252 organism as described herein. 3. Production of large quantities of crude phenylalanine ammonia lyase in the form of cell paste for Prof. Creed Abell at the University of Texas, Medical Branch, at Galveston,. 4. Production of a crude staphylococcal nuclease for the program of Dr. David Sachs, National Cancer Institute, Bethesda, Maryland. 5. Developmental studies and limited production of a crude cysteine desulfhydrase according to the protocols of Dr. J. Uren, Sidney Farber Cancer Center, Boston, Massachusetts. 6. Preliminary production studies on the agent produced by Culture FCRC 14, discovered in the CFL search program. 7. Developmental fermentation studies on the antitumor antibiotic, piperazinedione 593A [6], in preparation for production of quantities of this antibiotic to support clinical studies under the auspices of the National Cancer Institute.

Microbial reduction of the side-chain carbonyl of daunorubicin and N-acetyldaunorubicin.

Microorganisms reduced the side-chain carbonyl of daunorubicin to yield 13-dihydrodaunorubicin (daunorubicinol; daunomycinol). This microbial transformation occurred under aerobic conditions in agitated baffled shake flasks incubated at 37 degrees C. The microorganisms were first grown in a medium which supported dense growth. Daunorubicin-HCl was then added. Following a period of incubation, broths were adjusted to pH 10.0 and extracted with chloroform. Daunorubicinol was recovered and purified from the chloroform extracts by preparative TLC. Identity of the daunorubicinol was established by TLC and spectroscopy (UV-vis, IR, NMR, MS, CD and ORD). N-Acetyldaunorubicin was likewise reduced microbially to N-acetyldaunorubicinol. N-Acetyldaunorubicinol appears to be a new compound which is yet to be tested for antitumor activity.