Development Of Biotechnology Products Research Articles

Life cycle assessment for early-stage process optimization of microbial biosurfactant production using kinetic models-a case study on mannosylerythritol lipids (MEL).

Introduction: This study assesses the environmental impacts of mannosylerythritol lipids (MELs) production for process optimization using life cycle assessment (LCA). MELs are glycolipid-type microbial biosurfactants with many possible applications based on their surface-active properties. They are generally produced by fungi from the family of Ustilaginaceae via fermentation in aerated bioreactors. The aim of our work is to accompany the development of biotechnological products at an early stage to enable environmentally sustainable process optimization. Methods: This is done by identifying hotspots and potentials for improvement based on a reliable quantification of the environmental impacts. The production processes of MELs are evaluated in a cradle-to-gate approach using the Environmental Footprint (EF) 3.1 impact assessment method. The LCA model is based on upscaled experimental data for the fermentation and purification, assuming the production at a 10m³ scale. In the case analyzed, MELs are produced from rapeseed oil and glucose, and purified by separation, solvent extraction, and chromatography. Results: The results of the LCA show that the provision of substrates is a major source of environmental impacts and accounts for 20% of the impacts on Climate Change and more than 70% in the categories Acidification and Eutrophication. Moreover, 33% of the impacts on Climate Change is caused by the energy requirements for aeration of the bioreactor, while purification accounts for 42% of the impacts respectively. For the purification, solvents are identified as the main contributors in most impact categories. Discussion: The results illustrate the potentials for process optimization to reduce the environmental impacts of substrate requirements, enhanced bioreactor aeration, and efficient solvent use in downstream processing. By a scenario analysis, considering both experimental adaptations and prospective variations of the process, the laboratory development can be supported with further findings and hence efficiently optimized towards environmental sustainability. Moreover, the presentation of kinetic LCA results over the fermentation duration shows a novel way of calculating and visualizing results that corresponds to the way of thinking of process engineers using established environmental indicators and a detailed system analysis. Altogether, this LCA study supports and demonstrates the potential for further improvements towards more environmentally friendly produced surfactants.

The influence of varying concentrations of CO2 on the buildup of carbohydrates in microalgae biomass

Microalgae have gained popularity over the century due to their numerous intrinsic properties superior to higher plants, making them a potential target and feedstock for the development of biotechnological products in various fields. The storage of carbohydrates within microalgae cells positions them as a promising reservoir for biofuel production and a range of other valuable bioproducts, encompassing biological compounds, nutritional supplements, and more. Key determinants influencing microalgae carbohydrate levels comprise nutrient availability, light intensity, temperature, and CO2 concentrations. In this context, the CO2 concentration plays a key role, as it is one of the main factors influencing the photosynthetic processes. This study aimed to explore the impact of different CO2 concentrations on the carbohydrate profile of biomass sourced from Chlorella vulgaris sp. BB-2 and Scenedesmus quadicauda B-1. The findings revealed that a CO2 concentration of 2% v/v notably enhanced carbohydrate accumulation, reaching 75.5% for Chlorella vulgaris sp. BB-2 and 72.0% for Scenedesmus quadicauda B-1.

Molecular Identification and Characterization of Five Ganoderma Species from the Lower Volta River Basin of Ghana Based on Nuclear Ribosomal DNA (nrDNA) Sequences.

Ganoderma is a genus of biomedical fungus that is used in the development of numerous health products throughout the world. The Lower Volta River Basin of Ghana is an undulating land surface covered by extensive vegetation and water bodies and is rich in polypore mushrooms resembling various members of the Ganoderma genus. Despite the extensive biopharmaceutical benefits of Ganoderma spp., the isolates from the Lower Volta River Basin have not been properly characterized, thus limiting their use in the development of biotechnological products. In this study, Ganoderma spp. collected from the Lower Volta River Basin were genetically analyzed using the nuclear ribosomal sequences, the internal transcribed spacer 2 (ITS 2), the complete internal transcribed spacer (ITS), and the nuclear large subunit (nLSU). Blastn search and sequence analysis revealed that the sample we coded as Ganoderma LVRB-2 belongs to G. mbrekobenum, whereas Ganoderma LVRB-1, Ganoderma LVRB-14, and Ganoderma LVRB-16 belong to the species G. enigmaticum. Our analysis further demonstrates that Ganoderma LVRB-17 belongs to the species G. resinaceum. Thus, the five samples collected in the present study were positioned in three different distinct groups, namely G. mbrekobenum, G. enigmaticum, and G. resinaceum. The current data may serve as reference points for future studies.

Regenerative potential and clinical application of mesenchymal stem cell-derived exosomes (review)

For more than 50 years, mesenchymal stem cells have been extensively studied as a therapeutic agent in the treatment of various diseases. It became clear that MSC-derived secretome including the growth factors, cytokines, microvesicles and exosomes are the major drivers in the realization of beneficial effect of MSC-based therapy. Exosomes play an important role in the organism homeostasis and diseases development working as a vehicle for the transfer of the signaling and regulatory molecules between cells. Exosomes size, stability, cargo content that reflect the physiological state of parent cells make them an attractive new tool for regenerative medicine. Cell-free therapy or cell therapy 2.0 are being developed. Here, we review the molecular profile of exosomes derived from different MSC sources and their biological properties, the results of clinical application of MSC-derived exosomes in the of treatment COVID-19, alopecia, skin aging and osteoarthritis, discuss what issues exist in the development and application of a new biomedical product. The purpose of this study was to analyze the literature data on the regenerative potential and clinical application of exosomes derived from mesenchymal stem cells. Materials and methods. An analytical review of literature data was conducted using the information analysis of Medline (PubMed), Web of Science and Scopus databases, Google Scholar and the Cochrane Central Register of Controlled Trials (CENTRAL) and other sources until 2022 inclusive using the keywords: «exosomes», «mesenchymal stem cells», «cell-free therapy», «secretome», «miRNA» Results. In this review, we consider the molecular profile of exosomes derived from different MSC sources and their biological properties, the results of clinical application of MSC-derived exosomes in the treatment of COVID-19, alopecia, skin aging and osteoarthritis, discuss what issues exist in the development and application of a new biomedical product. Conclusion. The study, research and development of biotechnological products based on exosomes from different stem cell types are new stages in the development of regenerative medicine. Understanding the unique biological properties of MSCs derived from various tissue sources is one of the keys to develop effective exosomes-based biotechnological products to address specific medical goals.

Frontiers in nonviral delivery of small molecule and genetic drugs, driven by polymer chemistry and machine learning for materials informatics.

Materials informatics (MI) has immense potential to accelerate the pace of innovation and new product development in biotechnology. Close collaborations between skilled physical and life scientists with data scientists are being established in pursuit of leveraging MI tools in automation and artificial intelligence (AI) to predict material properties in vitro and in vivo. However, the scarcity of large, standardized, and labeled materials data for connecting structure-function relationships represents one of the largest hurdles to overcome. In this Highlight, focus is brought to emerging developments in polymer-based therapeutic delivery platforms, where teams generate large experimental datasets around specific therapeutics and successfully establish a design-to-deployment cycle of specialized nanocarriers. Three select collaborations demonstrate how custom-built polymers protect and deliver small molecules, nucleic acids, and proteins, representing ideal use-cases for machine learning to understand how molecular-level interactions impact drug stabilization and release. We conclude with our perspectives on how MI innovations in automation efficiencies and digitalization of data-coupled with fundamental insight and creativity from the polymer science community-can accelerate translation of more gene therapies into lifesaving medicines.

Search for new yeast strains to improve the feed base

Currently, yeast cultures are used in a large number of industry areas. The use of microbial biomass as a protein, probiotic, enzyme additive requires a comprehensive study of its composition, digestibility, digestibility, toxicity testing, not only of living cells, but also of their metabolic products. The aim of the work was to determine the potential of isolated microorganisms for the development of biotechnological products of microbial synthesis. The result of the studies were 2,356 strains of bacteria and fungi isolated from the gastrointestinal tract of agricultural animals. Of these, 1,641 were classified as opportunistic bacteria and excluded from the study. Of these, 12 isolates of yeast of the Saccharomyces class were selected for further studies after the toxicity was determined. In our studies, isolated yeast isolates had the ability to ferment glucose, dextrose, sucrose and mannose in more than 83% of samples; fructose, inulin, esculin and citrate - more than 67%; galactose, raffinose and sorbose more than 50%. All the studied isolates were tested for the quantitative content of protein in the cells. Fluctuations in crude protein ranged from 37.14% to 46.05%, which suggests the possibility of increasing its content when enriching the growth medium during cultivation. The highest levels of lysine were observed in samples Sf 7, Sf 28, Cr 11 (4.91, 5.11, 5.07 g/100 g of SP, respectively), methionine in samples Sr 9, Cr 2, Cr 32 (4.83, 6.78, 5.42 g/100 g of SP, respectively), and threonine in samples Sf 28, Sf 45, Cr 11 (6,08, 6,22, 5,71 g/ 100 g SP respectively).High enzymatic activity, high-grade amino acid composition, intermediate position between vegetable and animal protein in further research makes it possible to use the isolated microorganisms as a feed product in animal husbandry.

Green Synthesis and Characterization of Libyan Propolis Nanoparticles and its Biological Activity

The ever-increasing demand for natural products and biotechnology, derived from bees and ultra-modernization of various analytical devices, has facilitated the rational and planned development of biotechnology products with a focus on human health to treat chronic and neglected diseases. This study aimed to prepare, characterize and examine the stability and evaluation of the antioxidant and the antibacterial activity of Libyan propolis. Propolis Nanoparticles PNP were prepared using particle size reduction, then Transmission Electron Microscope (TEM) at a magnification of X 25000, was used for accurate evaluation of the size distribution of NPs. Three different concentration (10, 5, 2.5 mg/ml) of propolis and nano-propolis powder were tested for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. The quantitative antioxidant activity test results using UV Spectrophotometer absorbance at 517 nm. The antibacterial activities of propolis and prepared nano propolis at different concentrations (10, 5 and 2.5mg/ml) were tested on bacterial strain, Klebsiella, human mouth, skin, and surface bacteria using cup cut diffusion method. The findings exhibited that the prepared propolis Nanoparticles (PNPs) were generally non-spherical with a size 100-200 nm. The PNP was a nano-sized particle around 316 nm in diameter. Zeta potential of PNP showed a negative surface charge value (− 48 mV) which was sufficiently high to avoid NPs aggregation. This value represents a stable and dispersed suspension of NPs and disables the tendency of aggregations in a short in period of time. Poly dispersity index (PdI) of synthetized PNP was used as a measurement of the size distribution. PdI values for PrNP were generally uniform with PdI 0.3 indicating monodispersity of the prepared systems. The propolis and PNPs displayed good antioxidant activity with inhibition percentage (77%, 46% and 18%) for propolis and (82%, 66% and 37%) for PNPs. Propolis nanoparticles showed to have more antibacterial effect compared to propolis. Libyan propolis nanoparticles has shown to be potential candidates as antioxidant and antibacterial agent.

A recombinant SARS-CoV-2 receptor-binding domain expressed in an engineered fungal strain of Thermothelomyces heterothallica induces a functional immune response in mice

Since the beginning of the COVID-19 pandemic, the development of effective vaccines against this pathogen has been a priority for the scientific community. Several strategies have been developed including vaccines based on recombinant viral protein fragments. The receptor-binding domain (RBD) in the S1 subunit of S protein has been considered one of the main targets of neutralizing antibodies. In this study we assess the potential of a vaccine formulation based on the recombinant RBD domain of SARS-CoV-2 expressed in the thermophilic filamentous fungal strain Thermothelomyces heterothallica and the hepatitis B virus (HBV) core protein. Functional humoral and cellular immune responses were detected in mice. To our knowledge, this is the first report on the immune evaluation of a biomedical product obtained in the fungal strain T. heterothallica. These results together with the intrinsic advantages of this expression platform support its use for the development of biotechnology products for medical purpose.

Pichia pastoris as a biological platform to produce recombinant proteins: relevance for development of biotechnological products in Colombia

The world market for compounds produced by biotechnological means is growing due to the search and implementation of cellular systems that allow the mass production of complex molecules with a specific biological activity. These range from drugs, to enzymes and proteins for diverse uses, such as academic research and the development of industrial processes. Pichia pastoris is a methylotrophic yeast that has been studied in recent decades for the expression and generation of recombinant proteins, because it has features that make it especially efficient, not only to host external DNA, but also to express it and, thus, produce a wide variety of molecules. In this study, the most important aspects related to the production of recombinant proteins are examined, by using P. pastoris as a model, from the most common expression strategy, to the aspects related to the cultivation at bioreactor scale and, by yielding high-value products. Some papers conducted, in Colombia, are also reviewed, as well as their approach and the current state of the expression system in the country's biotechnology and its barriers, by concluding that studies with P. pastoris are scarce and are mainly developed around a few academic centers.

Morphological and Molecular Identification of Entomopathogenic Fungi from Agricultural and Forestry Crops

Abstract A promising alternative for insect pest control in agriculture is the use of entomopathogenic fungi. The objectives of this work were to isolate and identify morphologically and molecularly strains of entomopathogenic fungi from crops of agricultural and forestry interest for the development of insect biocontrol technologies in Argentina. Three strains of Beauveria bassiana, and two strains of Metarhizium anisopliae were isolated and morphologically identified. Identity values greater than 99% with strains of B. bassiana and M. anisopliae were obtained in molecular databases. It was also confirmed by phylogenetic methods that the sequences obtained from these strains were positioned within the clade that contained the sequences of reference of B. bassiana and M. anisopliae respectively. These results deepen the knowledge of the mycobiota of Argentinian crops as a basis for the development of biotechnological products in the area of biological control.

The key role of terminators on the expression and post-transcriptional gene silencing of transgenes.

Transgenes have become essential to modern biology, being an important tool in functional genomic studies and also in the development of biotechnological products. One of the major challenges in the generation of transgenic lines concerns the expression of transgenes, which, compared to endogenes, are particularly susceptible to silencing mediated by small RNAs (sRNAs). Several reasons have been put forward to explain why transgenes often trigger the production of sRNAs, such as the high level of expression induced by commonly used strong constitutive promoters, the lack of introns, and features resembling viral and other exogenous sequences. However, the relative contributions of the different genomic elements with respect to protecting genes from the silencing machinery and their molecular mechanisms remain unclear. Here, we present the results of a mutagenesis screen conceived to identify features involved in the protection of endogenes against becoming a template for the production of sRNAs. Interestingly, all of the recovered mutants had alterations in genes with proposed function in transcription termination, suggesting a central role of terminators in this process. Indeed, using a GFP reporter system, we show that, among different genetic elements tested, the terminator sequence had the greatest effect on transgene-derived sRNA accumulation and that a well-defined poly(A) site might be especially important. Finally, we describe an unexpected mechanism, where transgenes containing certain intron/terminator combinations lead to an increase in the production of sRNAs, which appears to interfere with splicing.

Technological Mapping on the Use of Palygorskita Nanocompositals / Silver Nanoparticles as A Bactericide Agent with Views in Biotechnological Applications

The search for new nanostructured materials that have an antimicrobial activity and which may arise as an alternative in biotechnological applications has aroused great interest by the scientific community. The use of natural resources in the development of these materials becomes interesting not only because of their availability and low cost, but also because they are materials with low or no toxicity and properties of interest, such as palygorskite clay ( PAL), also called atapulgite. Thus, a new applicability is proposed with the use of this natural resource for the development of biotechnological products, such as the development of nanocomposites constituted by the incorporation of silver nanoparticles (AgNPs) in PAL for its use as bactericidal agent. The objective of the research was to carry out a prospective study on the basis of periodicals of Scopus, Web of Science and Scielo, as well as in the patent banks of the National Institute of Industrial Property (INPI), European Patent Office (Espacenet) and United States Patent and Trademark Offic (USPTO), from 2006 to 02/2017. From the results of articles and patents, a considerable number of articles and patents were found using the word "Palygorskite" or "Attapulgite". However, when the "Palygorskite or Attapulgite AND silver nanoparticle AND antimicrobial" and "Palygorskite or Attapulgite AND silver nanoparticle AND bactericidal" combinations were used, no article or patent has been found to date. Thus, the development of PAL / AgNPs nanocomposites for biotechnological applications can be very promising and innovative for the characteristics presented by both materials. Keywords: Nanocomposites; Palygorskite; Attapulgite; Silver of nanoparticles; Bactericidal agent.

MBSP1: a biosurfactant protein derived from a metagenomic library with activity in oil degradation

Microorganisms represent the most abundant biomass on the planet; however, because of several cultivation technique limitations, most of this genetic patrimony has been inaccessible. Due to the advent of metagenomic methodologies, such limitations have been overcome. Prevailing over these limitations enabled the genetic pool of non-cultivable microorganisms to be exploited for improvements in the development of biotechnological products. By utilising a metagenomic approach, we identified a new gene related to biosurfactant production and hydrocarbon degradation. Environmental DNA was extracted from soil samples collected on the banks of the Jundiaí River (Natal, Brazil), and a metagenomic library was constructed. Functional screening identified the clone 3C6, which was positive for the biosurfactant protein and revealed an open reading frame (ORF) with high similarity to sequences encoding a hypothetical protein from species of the family Halobacteriaceae. This protein was purified and exhibited biosurfactant activity. Due to these properties, this protein was named metagenomic biosurfactant protein 1 (MBSP1). In addition, E. coli RosettaTM (DE3) strain cells transformed with the MBSP1 clone showed an increase in aliphatic hydrocarbon degradation. In this study, we described a single gene encoding a protein with marked tensoactive properties that can be produced in a host cell, such as Escherichia coli, without substrate dependence. Furthermore, MBSP1 has been demonstrated as the first protein with these characteristics described in the Archaea or Bacteria domains.

ANALYSIS OF EXISTING BIOREACTORS WITH IMMOBILIZED MICROORGANISMS

This review article describes the current state of the industry of immobilized cells and the development of bioreactors with immobilized cells and carrier materials for immobilization. On the basis of literature analysis, a classification of constructions of bioreactors with immobilized cells is proposed, depending on the location of cellular aggregates: suspended particles, fixed particles and moving surfaces used with immobilized cells. The modern development of biotechnological production requires new approaches to the implementation of biosynthesis processes. The performance of bioreactors in the production of various target products depends on the efficiency of the use of biological agents, which depends on the process conditions. One of the ways to improve the performance of fermentation is cell immobilization, which provides the possibility of continuous processing, cell stability, reducing the cost of recovery, recycling and further processing. Immobilization of cells protects them from landslide efforts that may occur during the operation of the bioreactor. At the same time, the industrial use of immobilized cells is still limited and their further application requires a detailed analysis of the specific features of the designs of bioreactors with immobilized cells and carrier materials for immobilization. At present, there is a large variety of immobilization methods, but they can be conventionally divided into chemical, physical and mechanical. The most widespread mechanical method was the inclusion of cells in the composition of gels, membranes and fibers. Consequently, for the wider introduction of methods and equipment using immobilized cells in biotechnological and pharmaceutical industries, further research is required on how to immobilize cells on a variety of carriers.

Residues from the Brazilian pepper tree (Schinus terebinthifolia Raddi) processing industry: Chemical profile and antimicrobial activity of extracts against hospital bacteria

Schinus terebinthifolia Raddi is a plant used in folk medicine in the treatment of various diseases and has several biological potentials. Its fruit is used as condiment and has high demand in the spice market. In the present study extracts of different polarities prepared from residues from the Brazilian pepper tree processing industry were characterized chemically by gas chromatography/mass spectrometry (GC–MS) and negative-ion mode electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI(-)FT-ICR MS). The antibacterial activity of the extracts was evaluated against multidrug-resistant strains of hospital origin (Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Pseudomonas aeruginosa and Acinetobacter baumannii) and standard strains (ATCC). The apolar fractions (dichloromethane and hexane) presented triterpenes as main components and the polar extracts (methanol and hydroethanolic extracts) were characterized by high contents of phenolic compounds, especially gallotannins, gallic acid and flavonoids. The methanolic fraction and the hydroethanolic extract of the residues were the most active mainly against S. aureus (MIC 0.60–0.90 mg/mL), E. faecium and E. faecalis (MIC 1.20–2.10 mg/mL). These results demonstrate the richness of bioactive compounds present in the residues and indicate a possible application of this material for the development of biotechnological products with potential against multidrug-resistant bacteria.

Case Study in International Cooperation: Cuba's Molecular Immunology Center and Roswell Park Cancer Institute

In 1961, the USA severed diplomatic relations with Cuba, and in 1962 an embargo was imposed on trade and financial relations with that country. It was not until five decades later that the USA and Cuba would reestablish relations. This opened the way for the New York State Trade Mission to Cuba in April 2015, during which Cuba's Molecular Immunology Center and Buffalo, New York's Roswell Park Cancer Institute signed a formal agreement that would set in motion biotechnology research collaboration to address one of the most important causes of death in both countries. Significant research from Cuba led to this groundbreaking collaboration. The purpose of this paper is to discuss the development of this cooperation, from the Molecular Immunology Center's initial investigations, through the opening of a phase I clinical trial at Roswell Park Cancer Institute with therapies developed at the Center. This cooperation was responsible for the first clinical trial for CIMAvax-EGF involving advanced-stage non-small cell lung cancer patients in the USA. A license was also approved by the US Department of the Treasury's Office of Foreign Assets Control authorizing a commercial partnership for development of biotechnology products, combining the cancer research efforts of both institutions. This unusual collaboration between Cuba and the USA-the US economic embargo and travel restrictions not withstanding-opens good prospects for expanded medical research between the two countries. While political and logistical challenges remain, the shared mission and dedication of these Cuban and US scientists points the way towards relationships that can lead to development, testing, approval and use of promising new therapies for cancer patients. KEYWORDS Biotechnology, clinical trials, cancer vaccines, cancer immunotherapy, non-small cell lung cancer, NSCLC, Cuba, USA.

Bioaccumulation of Lithium (Li2CO3) in Mycelia of the Culinary-Medicinal Oyster Mushroom, Pleurotus ostreatus (Agaricomycetes).

Pleurotus ostreatus is a white-rot mushroom that bioaccumulates metals in basidiocarps and vegetative mycelia. This fungus has been used in soil and water bioremediation of several heavy metals; however, there are few studies of lithium mycelial bioaccumulation for pharmacological use. The aim of this study was to evaluate lithium bioaccumulation in P. ostreatus mycelia grown in a liquid malt extract cultivation medium with Li2CO3 or LiCl. Each lithium source was added to the medium to obtain a concentration of 0, 5, 10, 15, 20, 25, 30, 40, 50, 100, or 200 mg · L-1 lithium. The highest bioaccumulation of lithium in mycelia was 1575.29 μg · g-1 upon treatment with 40 mg · L-1 Li2CO3. P. ostreatus mycelia produce biomass and bioaccumulate both lithium sources, but more lithium bioaccumulates when in the form of Li2CO3. This study provides a prospective for the development of biotechnological products with high aggregate values and alternative ways to deliver lithium and eventually other salts for pharmacological use.

Case Study in International Cooperation: Cuba's Molecular Immunology Center and Roswell Park Cancer Institute.

In 1961, the USA severed diplomatic relations with Cuba, and in 1962 an embargo was imposed on trade and financial relations with that country. It was not until five decades later that the USA and Cuba would reestablish relations. This opened the way for the New York State Trade Mission to Cuba in April 2015, during which Cuba's Molecular Immunology Center and Buffalo, New York's Roswell Park Cancer Institute signed a formal agreement that would set in motion biotechnology research collaboration to address one of the most important causes of death in both countries. Significant research from Cuba led to this groundbreaking collaboration. The purpose of this paper is to discuss the development of this cooperation, from the Molecular Immunology Center's initial investigations, through the opening of a phase I clinical trial at Roswell Park Cancer Institute with therapies developed at the Center. This cooperation was responsible for the first clinical trial for CIMAvax-EGF involving advanced-stage non-small cell lung cancer patients in the USA. A license was also approved by the US Department of the Treasury's Office of Foreign Assets Control authorizing a commercial partnership for development of biotechnology products, combining the cancer research efforts of both institutions. This unusual collaboration between Cuba and the USA-the US economic embargo and travel restrictions not withstanding-opens good prospects for expanded medical research between the two countries. While political and logistical challenges remain, the shared mission and dedication of these Cuban and US scientists points the way towards relationships that can lead to development, testing, approval and use of promising new therapies for cancer patients. KEYWORDS Biotechnology, clinical trials, cancer vaccines, cancer immunotherapy, non-small cell lung cancer, NSCLC, Cuba, USA.

The role of standardization at the interface of product and process development in biotechnology

R&D stands for Research and Development and while research is essential for new product development in biotechnology, the development and its integration with research (the transfer from research to development) is underexplored. Without efficient and successful process development, biotech companies would not sustain in the long run as process development is a necessary condition en route to industrial commercialization. Based on qualitative interviews with 31 biotech companies and experts, we test a framework with technological, operational and organizational boundary conditions influencing the transfer between product and process development. Our results uncover two additional dimensions: relational and market determinants. We further identify uncertainties in the transfer and investigate if standardization can mitigate these uncertainties and eventually facilitate the integration of product and process development. We find that standardization is a beneficial mechanism for successful integration of the front end of process development activities. The present investigation contributes to the understanding of standards as a knowledge and technology transfer instrument for complex and critical development activities.

Mating of 2 Laboratory Saccharomyces cerevisiae Strains Resulted in Enhanced Production of 2-Phenylethanol by Biotransformation of L-Phenylalanine

2-Phenylethanol (2-PE) is an aromatic alcohol with a rosy scent which is widely used in the food, fragrance, and cosmetic industries. Promising sources of natural 2-PE are microorganisms, especially yeasts, which can produce 2-PE by biosynthesis and biotransformation. Thus, the first challenging goal in the development of biotechnological production of 2-PE is searching for highly productive yeast strains. In the present work, 5 laboratory Saccharomyces cerevisiae strains were tested for the production of 2-PE. Thereafter, 2 of them were hybridized by a mating procedure and, as a result, a new diploid, S. cerevisiae AM1-d, was selected. Within the 72-h batch culture in a medium containing 5 g/L of <smlcap>L</smlcap>-phenylalanine, AM1-d produced 3.83 g/L of 2-PE in a shaking flask. In this way, we managed to select the diploid S. cerevisiae AM1-d strain, showing a 3- and 5-fold increase in 2-PE production in comparison to parental strains. Remarkably, the enhanced production of 2-PE by the hybrid of 2 yeast laboratory strains is demonstrated here for the first time.