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Characterization of an echinocandin B-producing strain blocked for sterigmatocystin biosynthesis reveals a translocation in the stcW gene of the aflatoxin biosynthetic pathway (2000)

Hodges, R L ; Kelkar, H S ; Xuei, X ; [et al.]

Springer

Journal of industrial microbiology and biotechnology 25 (2000), S. 333-341

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ISSN: 1476-5535

Keywords: Keywords: Aspergillus nidulans; aflatoxin; sterigmatocystin; mutagenesis; translocation; echinocandin B

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: Echinocandin B (ECB), a lipopolypeptide used as a starting material for chemical manufacture of the anti-Candida agent LY303366, is produced by fermentation using a strain of Aspergillus nidulans. In addition to ECB, the wild-type strain also produces a significant level of sterigmatocystin (ST), a potent carcinogen structurally related to the aflatoxins. Characterization of a mutant designated A42355-OC-1 (OC-1), which is blocked in ST biosynthesis, was the result of a chromosomal translocation. The chromosomal regions containing the breakpoints of the translocation were isolated and DNA sequencing and PCR analysis of the chromosomal breakpoints demonstrated the translocation occurred within the stcW gene of the ST biosynthetic pathway, resulting in disruption of the open reading frame for this gene. Biochemical feeding studies indicate the involvement of this gene product in the conversion of averufin to 1-hydroxy versicolorone. This work demonstrates an effective synergy between classical strain improvement methods and molecular genetics. Journal of Industrial Microbiology & Biotechnology (2000) 25, 333–341.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1038/sj.jim.7000076

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Mutants of a lovastatin-hyperproducingAspergillus terreus deficient in the production of sulochrin (1991)

Vinci, V. A. ; Hoerner, T. D. ; Coffman, A. D. ; [et al.]

Springer

Journal of industrial microbiology and biotechnology 8 (1991), S. 113-119

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ISSN: 1476-5535

Keywords: Microtiter fermentation ; Lovastatin ; Polyketide ; Strain improvement ; Screening

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: Summary A lovastatin-hyperproducing culture ofAspergillus terreus was shown to produce several co-metabolites extracted from whole broth. The predominant co-metabolite was the benzophenone, sulochrin, reported to arise from a polyketide biosynthetic pathway. This compound was targeted for elimination by classical mutagenesis and screening. A surface culture method employing microtiter, plates was used to ferment mutants for the primary screen. Qualitative determinations of lovastatin and sulochrin production were achieved by high-performance thin-layer chromatography. A mutant, strain AH6, which produced lovastatin titers equivalent to the parent culture and no detectable sulochrin was isolated. In addition, a lovastatin-hyperproducing mutant designated CB4 was capable of producing 16% more lovastatin and 30% less sulochrin than the parent culture in shake flask fermentations. In a pilot-scale 250-gallon fermentation, strain CB4 gave a 20% increase in lovastatin titer while producing 83% less sulochrin than the parent culture.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01578762

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Improvement of microbial strains and fermentation processes (2000)

Parekh, S. ; Vinci, V. A. ; Strobel, R. J.

Springer

Applied microbiology and biotechnology 54 (2000), S. 287-301

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ISSN: 1432-0614

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: Abstract Improvement of microbial strains for the over-production of industrial products has been the hallmark of all commercial fermentation processes. Conventionally, strain improvement has been achieved through mutation, selection, or genetic recombination. Over-production of primary or secondary metabolites is a complex process, and successful development of improved strains requires a knowledge of physiology, pathway regulation and control, and the design of creative screening procedures. In addition, it requires mastery of the fermentation process for each new strain, as well as sound engineering know-how for media-optimization and the fine-tuning of process conditions. This review focuses on the various options that may be employed to improve microbial strains and addresses the complex problems of screening, the tools and technology behind the selection of targeted organisms, and the importance of process optimization. Furthermore, this review discusses new and emerging technologies and designing optimized media for tracking mutants with enhanced productivity or other desired attributes.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s002530000403

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