The influence of medium design on lovastatin production and pellet formation with a high-producing mutant of Aspergillus terreus in submerged cultures
TL;DR: Plackett–Burman screening, factorial designs, and second-order response surface methodology (RSM) for medium optimization were employed for lovastatin production by a high-producing mutant of Aspergillus terreus, and the method used was effective in screening for nutritional requirements in a limited number of experiments.
About: This article is published in Process Biochemistry.The article was published on 2003-04-30. It has received 114 citations till now. The article focuses on the topics: Aspergillus terreus & Corn steep liquor.
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Chinese Academy of Sciences1, Kunming Institute of Botany2, University of Montpellier3, University of Mauritius4, Chiang Mai University5, Iloilo Science and Technology University6, Mae Fah Luang University7, Thailand Ministry of Agriculture and Cooperatives8, World Agroforestry Centre9, Aix-Marseille University10, Ohio State University11, VIT University12, Shenzhen University13, University of Electronic Science and Technology of China14, University of Santo Tomas15, University of Science and Technology16, University of Agricultural Sciences, Dharwad17, University of the Philippines Visayas18, Ramakrishna Mission19
TL;DR: This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology and provides a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products.
Abstract: Fungi are an understudied, biotechnologically valuable group of organisms. Due to
the immense range of habitats that fungi inhabit, and the consequent need to compete against a diverse array of other fungi, bacteria, and animals, fungi have developed numerous survival mechanisms. The unique attributes of fungi thus herald great promise for their application in biotechnology and industry. Moreover, fungi can be grown with relative ease, making production at scale viable. The search for fungal biodiversity, and the construction of a living fungi collection, both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products. This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology. We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers. We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products. Fungi have provided the world with penicillin, lovastatin, and other globally significant medicines, and they remain an untapped resource with enormous industrial potential.
404 citations
TL;DR: Advances in the biochemistry and genetics of lovastatin have allowed the development of new methods for the production of simvastatin, the second leading statin in the market, which is a Lovastatin semisynthetic derivative.
Abstract: Statins are a group of extremely successful drugs that lower cholesterol levels in blood; decreasing the risk of heath attack or stroke. In recent years, statins have also been reported to have other biological activities and numerous potential therapeutic uses. Natural statins are lovastatin and compactin, while pravastatin is derived from the latter by biotransformation. Simvastatin, the second leading statin in the market, is a lovastatin semisynthetic derivative. Lovastatin is mainly produced by Aspergillus terreus strains, and compactin by Penicillium citrinum. Lovastatin and compactin are produced industrially by liquid submerged fermentation, but can also be produced by the emerging technology of solid-state fermentation, that displays some advantages. Advances in the biochemistry and genetics of lovastatin have allowed the development of new methods for the production of simvastatin. This lovastatin derivative can be efficiently synthesized from monacolin J (lovastatin without the side chain) by a process that uses the Aspergillus terreus enzyme acyltransferase LovD. In a different approach, A. terreus was engineered, using combinational biosynthesis on gene lovF, so that the resulting hybrid polyketide synthase is able to in vivo synthesize 2,2-dimethylbutyrate (the side chain of simvastatin). The resulting transformant strains can produce simvastatin (instead of lovastatin) by direct fermentation.
171 citations
Book•
10 Aug 2009
TL;DR: Fractional Factorial Design Examples: The basics of fractional factorial designs are discussed in detail in this article, where the authors present an analysis of full-factorial experiments with two-level factors.
Abstract: Full Factorial Designs- to Full Factorial Designs with Two-Level Factors- Analysis of Full Factorial Experiments- Common Randomization Restrictions- More Full Factorial Design Examples- Fractional Factorial Designs- Fractional Factorial Designs: The Basics- Fractional Factorial Designs for Estimating Main Effects- Designs for Estimating Main Effects and Some Two-Factor Interactions- Resolution V Fractional Factorial Designs- Augmenting Fractional Factorial Designs- Fractional Factorial Designs with Randomization Restrictions- More Fractional Factorial Design Examples- Additional Topics- Response Surface Methods and Second-Order Designs- Special Topics Regarding the Design- Special Topics Regarding the Analysis- Appendices and Tables- Upper Percentiles of t Distributions, t- Upper Percentiles of F Distributions, F- Upper Percentiles for Lenth t Statistics, and- Computing Upper Percentiles for Maximum Studentized Residual- Orthogonal Blocking for Full 2 Factorial Designs- Column Labels of Generators for Regular Fractional Factorial Designs- Tables of Minimum Aberration Regular Fractional Factorial Designs- Minimum Aberration Blocking Schemes for Fractional Factorial Designs- Alias Matrix Derivation- Distinguishing Among Fractional Factorial Designs
152 citations
Cites background from "The influence of medium design on l..."
...Lai et al. (2003) report that in their next experiment they fixed the levels for factors B and G and added one new factor, Glycerol....
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TL;DR: The physiology of the Aspergillus such as life cycle, physiological responses and signal transductions, and carbon and nitrogen metabolisms are presented in this chapter.
Abstract: Publisher Summary This chapter discusses the physiology and biotechnology of Aspergillus species. The genus Aspergillus is found worldwide and consists of more than 180 officially recognized species. Molecular and genetic studies of Aspergillus species tend to concentrate on four thoroughly investigated species: A. nidulans, A. niger, A. oryzae, and A. fumigatus. The physiology of the Aspergillus such as life cycle, physiological responses and signal transductions, and carbon and nitrogen metabolisms are presented in this chapter. Most Aspergillus species, except A. fumigatus, have both sexual and asexual processes for spore duplication. A few, including A. nidulans, are also able to reproduce via a parasexual cycle. The capacities of microbial species to survive and respond physiologically to changes in their environment enable these species to exist under a broad range of conditions. Several signaling pathways are involved in Aspergillus cell growth and differentiation, and indicate links between cell developments to metabolite biosynthesis. The molecular biology of Aspergillus is also explained with the help of its gene expression, and by discussing the molecular biology approach of production of protein by Aspergillus species. The chapter presents the industrial application of the Aspergillus species such as citric acid production, production of extracellular enzymes, role of Aspergillus in the process of biotransformation, production of secondary metabolites, environmental applications, and production of other industrial products.
140 citations
TL;DR: In this article, the authors investigated the effects of fermentation time, temperature and broth content on mycelial growth in terms of dry cell weight (DCW) and extracellular polysaccharide content (EPC) produced by the fungus Boletus spp. in submerged fermentation.
120 citations
References
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Book•
01 Jan 1978
TL;DR: This paper used external reference distribution to compare two means and compared more than two treatment means, and compared the effects of different means and treatments in the United States of America, using the Declaration of Independence as an example.
Abstract: Science and Statistics. COMPARING TWO TREATMENTS. Use of External Reference Distribution to Compare Two Means. Random Sampling and the Declaration of Independence. Randomization and Blocking with Paired Comparisons. Significance Tests and Confidence Intervals for Means, Variances, Proportions and Frequences. COMPARING MORE THAN TWO TREATMENTS. Experiments to Compare k Treatment Means. Randomized Block and Two--Way Factorial Designs. Designs with More Than One Blocking Variable. MEASURING THE EFFECTS OF VARIABLES. Empirical Modeling. Factorial Designs at Two Levels. More Applications of Factorial Designs. Fractional Factorial Designs at Two Levels. More Applications of Fractional Factorial Designs. BUILDING MODELS AND USING THEM. Simple Modeling with Least Squares (Regression Analysis). Response Surface Methods. Mechanistic Model Building. Study of Variation. Modeling Dependence: Times Series. Appendix Tables. Index.
4,153 citations
2,729 citations
01 May 1979
406 citations
"The influence of medium design on l..." refers methods in this paper
...Various treatments in a series of experiments were developed or generated according to several standard texts and software on designing experiments [18,19]....
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TL;DR: Mycelial microorganisms are exploited extensively in the commercial production of a wide range of secondary metabolites, though problems are associated with the culture of each morphological type, and the methodology for inducing pellet formation and the type of pellets produced are an important consideration for effective metabolite production.
203 citations
"The influence of medium design on l..." refers background in this paper
...To produce secondary metabolites, the uncertainties came from lack of knowledge dealing with the sophisticated interactions of environments with microorganisms [12]....
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TL;DR: In this article, the effect of veratryl alcohol and yeast extract concentration, time of cultivation and agitation speed were evaluated by factorial analysis to select variables for optimizing the production of laccases.
141 citations
"The influence of medium design on l..." refers methods in this paper
...Here, we combined response surface methodology (RSM) [13] with experimental designs to identify important ingredients and to evaluate their relative significance in a limited number of experiments....
[...]
...Plackett /Burman screening, factorial designs, and second-order response surface methodology (RSM) for medium optimization were employed for lovastatin production by a high-producing mutant of Aspergillus terreus ....
[...]
...Here, we combined response surface methodology (RSM) [13] with experimental designs to identify important ingredients and to evaluate their relative significance in a limited number of experiments....
[...]