Publications by authors named "Frank V Ritacco"

5 Publications

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Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies.

Biotechnol Prog 2018 11 5;34(6):1407-1426. Epub 2018 Oct 5.

Biologics Process Development, Bristol-Myers Squibb, Pennington, New Jersey, United States.

The culture of Chinese Hamster Ovary (CHO) cells for modern industrial applications, such as expression of recombinant proteins, requires media that support growth and production. Such media must support high viable cell densities while also stimulating the synthesis and extracellular transport of biologic products. Early media development efforts in this area yielded basic formulations to sustain growth, viability, and cellular function, albeit comprising animal sourced components, and complex constituents used in batch culture mode. Subsequent improvements included the development of serum-free and chemically defined (CD) media, the identification of critical nutrients, growth factors, and potentially inhibitory or toxic cellular metabolites, and the use of fed-batch and perfusion culture techniques to optimize nutrient delivery while minimizing accumulation of unwanted waste products. This review is comprised of sections covering milestones in the evolution of mammalian cell culture media, nutrient composition and formulation requirements, optimization strategies, consistency and scalability of powder and liquid media preparation for industrial applications, and key recent advances driving progress in CHO cell culture medium design and development. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1407-1426, 2018.
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http://dx.doi.org/10.1002/btpr.2706DOI Listing
November 2018

Molecular and phenotypic comparison of phaeochromycin-producing strains of Streptomyces phaeochromogenes and Streptomyces ederensis.

J Ind Microbiol Biotechnol 2008 Sep 17;35(9):931-45. Epub 2008 May 17.

Wyeth Research, Pearl River, NY, USA.

Streptomyces strain LL-P018 produces the phaeochromycins, novel anti-inflammatory polyketides. This organism was identified as a strain of Streptomyces phaeochromogenes by physiological and genetic taxonomic analysis. In order to gain greater taxonomic perspective, LL-P018 was compared to related strains from major culture collections by 16S rRNA gene sequence, ribotype, HPLC-MS metabolite profile, and rpoB sequence. Using BioNumerics software, genetic and chemical fingerprint data were integrated via multivariate cluster analysis into a single, robust comparison. Based upon this analysis, strain LL-P018 is very closely related to the type strains of both S. phaeochromogenes and Streptomyces ederensis, indicating that these two types may in fact represent a single species. This novel comparative multi-cluster analysis is most useful for clarifying relationships between closely related species.
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http://dx.doi.org/10.1007/s10295-008-0367-0DOI Listing
September 2008

Phaeochromycins A-E, anti-inflammatory polyketides isolated from the soil actinomycete Streptomyces phaeochromogenes LL-P018.

J Nat Prod 2005 Aug;68(8):1262-5

Department of Chemical & Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA.

Five new polyketide metabolites, phaeochromycins A-E (1-5), were isolated from an actinomycete designated Streptomyces phaeochromogenes LL-P018, cultured from a soil sample collected from a riverbank in Westevenger, Germany. Phaeochromycins A and C were found to be weak inhibitors of MAPKAP kinase-2 (IC50 = 39 and 130 microM, respectively). The structures of the compounds were determined by spectroscopic analysis, primarily two-dimensional NMR, and revealed that phaeochromycins A, B, C, and E were octaketides, elaborated from a C4 starter unit, related to shunt products of the actinorhodin pathway, namely, mutactin, dehydromutactin, SEK34b, and BSM1. Phaeochromycin D (4) is an unusual partially cyclized degraded octaketide intermediate.
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http://dx.doi.org/10.1021/np0500629DOI Listing
August 2005

Production of novel rapamycin analogs by precursor-directed biosynthesis.

Appl Environ Microbiol 2005 Apr;71(4):1971-6

Natural Products, Wyeth Research, 401 North Middletown Road, Building 205, Room 465, Pearl River, NY 10965, USA.

The natural product rapamycin, produced during fermentation by Streptomyces hygroscopicus, is known for its potent antifungal, immunosuppressive, and anticancer activities. During rapamycin biosynthesis, the amino acid l-pipecolate is incorporated into the rapamycin molecule. We investigated the use of precursor-directed biosynthesis to create new rapamycin analogs by substitution of unusual l-pipecolate analogs in place of the normal amino acid. Our results suggest that the l-pipecolate analog (+/-)-nipecotic acid inhibits the biosynthesis of l-pipecolate, thereby limiting the availability of this molecule for rapamycin biosynthesis. We used (+/-)-nipecotic acid in our precursor-directed biosynthesis studies to reduce l-pipecolate availability and thereby enhance the incorporation of other pipecolate analogs into the rapamycin molecule. We describe here the use of this method for production of two new sulfur-containing rapamycin analogs, 20-thiarapamycin and 15-deoxo-19-sulfoxylrapamycin, and report measurement of their binding to FKBP12.
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http://dx.doi.org/10.1128/AEM.71.4.1971-1976.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1082568PMC
April 2005

Novel sulfur-containing rapamycin analogs prepared by precursor-directed biosynthesis.

Org Lett 2003 Jul;5(14):2385-8

Department of Chemical & Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA.

[reaction: see text] Two novel sulfur-containing analogs of the immunosuppressive natural product rapamycin (1) were obtained by feeding cultures of Streptomyces hygroscopicus with l-nipecotic acid (4) and either (S)-1,3-thiazane-4-carboxylic acid (5) or (S)-1,4-thiazane-3-carboxylic acid (6). The structures of the two new compounds, 20-thiarapamycin (2) and 15-deoxo-19-sulfoxylrapamycin (3), were determined by spectroscopic methods.
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http://dx.doi.org/10.1021/ol034591kDOI Listing
July 2003