scholarly journals Enhancing Saccharomyces cerevisiae Taxane Biosynthesis and Overcoming Nutritional Stress-Induced Pseudohyphal Growth

2022 ◽  
Vol 10 (1) ◽  
pp. 163
Author(s):  
Laura Ellen Walls ◽  
José L. Martinez ◽  
Leonardo Rios-Solis
Keyword(s):  
Synthetic Biology ◽  
Yeast Extract ◽  
Stress Responses ◽  
State Of The Art ◽  
Scale Up ◽  
Nutritional Stress ◽  
Filamentous Growth ◽  
Economic Benefits ◽  
Industrial Scale ◽  
Enhanced Production

The recent technological advancements in synthetic biology have demonstrated the extensive potential socio-economic benefits at laboratory scale. However, translations of such technologies to industrial scale fermentations remains a major bottleneck. The existence and lack of understanding of the major discrepancies in cultivation conditions between scales often leads to the selection of suboptimal bioprocessing conditions, crippling industrial scale productivity. In this study, strategic design of experiments approaches were coupled with state-of-the-art bioreactor tools to characterize and overcome nutritional stress for the enhanced production of precursors to the blockbuster chemotherapy drug, Taxol, in S. cerevisiae cell factories. The batch-to-batch variation in yeast extract composition was found to trigger nutritional stress at a mini-bioreactor scale, resulting in profound changes in cellular morphology and the inhibition of taxane production. The cells shifted from the typical budding morphology into striking pseudohyphal cells. Doubling initial yeast extract and peptone concentrations (2×YP) delayed filamentous growth, and taxane accumulation improved to 108 mg/L. Through coupling a statistical definitive screening design approach with the state-of-the-art high-throughput micro-bioreactors, the total taxane titers were improved a further two-fold, compared to the 2×YP culture, to 229 mg/L. Filamentous growth was absent in nutrient-limited microscale cultures, underlining the complex and multifactorial nature of yeast stress responses. Validation of the optimal microscale conditions in 1L bioreactors successfully alleviated nutritional stress and improved the titers to 387 mg/L. Production of the key Taxol precursor, T5αAc, was improved two-fold to 22 mg/L compared to previous maxima. The present study highlights the importance of following an interdisciplinary approach combining synthetic biology and bioprocessing technologies for effective process optimization and scale-up.

scholarly journals Photovoltaics Enabling Sustainable Energy Communities: Technological Drivers and Emerging Markets

Energies ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1862
Author(s):  
Alexandros-Georgios Chronis ◽  
Foivos Palaiogiannis ◽  
Iasonas Kouveliotis-Lysikatos ◽  
Panos Kotsampopoulos ◽  
Nikos Hatziargyriou
Keyword(s):  
State Of The Art ◽  
Research Question ◽  
Economic Benefits ◽  
Energy Market ◽  
Small Scale ◽  
Local Energy ◽  
Community Members ◽  
Open Research ◽  
Energy Community

In this paper, we investigate the economic benefits of an energy community investing in small-scale photovoltaics (PVs) when local energy trading is operated amongst the community members. The motivation stems from the open research question on whether a community-operated local energy market can enhance the investment feasibility of behind-the-meter small-scale PVs installed by energy community members. Firstly, a review of the models, mechanisms and concepts required for framing the relevant concepts is conducted, while a clarification of nuances at important terms is attempted. Next, a tool for the investigation of the economic benefits of operating a local energy market in the context of an energy community is developed. We design the local energy market using state-of-the-art formulations, modified according to the requirements of the case study. The model is applied to an energy community that is currently under formation in a Greek municipality. From the various simulations that were conducted, a series of generalizable conclusions are extracted.

scholarly journals THIAMINE – INDUCED FORMATION OF THE MONOPYRROLE MOIETY OF PRODIGIOSIN

2007 ◽  
Vol 4 (4) ◽  
pp. 622-627 ◽  
Author(s):  
Baghdad Science Journal
Keyword(s):  
Serratia Marcescens ◽  
Yeast Extract ◽  
Type Strain ◽  
The Other ◽  
Red Pigment ◽  
Enhanced Production ◽  
Pyrimidine Moiety ◽  
Glycerol Medium

Thiamine stimulates the production of a red pigment , which is chromatographically and spectrophotometrically identical to prodigiosin , by growing cultures of serratia marcescens mutant 9-3-3 . this mutant is blocked in the formation of 2- methyl -3- amyl pyrorol( MAP),the monopyrrole moiety of prodigiosin , but accumulates 4-methoxy-2, 2-bipyrrole -5- carboxaldehyde (MBC) and can couple this compound with( MAP) to form prodigiosin . Addition of thiamine caused production of( MAP) , and as little as 0.02 mg of thiamine / ml in peptone- glycerol medium stimulated production of measurable amounts of prodigiosin. Phosphate saltes and another type of peptone decreased the thiamine- induced formation of prodigiosin ,yeast extract and glycerol enhanced formation of this substance. Thiamine also enhanced production of prodigiosin by wiled – type Strain Nima of S. marcescens . The pyrimidine moiety of thiamine was also 10% as effective as the vitamin ; the thiazol moiety only 4% , and the two moieties together , 25% . Thiamine did not stimulate production of prodigiosin biosynthesis as strain 9-3-3 . This is not surprising since strain 9-3-3 originated as a result of two mutational events one event may involve thiamine directly , and the other may involve the biosynthesis of( MAP).

scholarly journals Changes in Oxygen Availability during Glucose-Limited Chemostat Cultivations of Penicillium chrysogenum Lead to Rapid Metabolite, Flux and Productivity Responses

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 45
Author(s):  
Qi Yang ◽  
Wenli Lin ◽  
Jiawei Xu ◽  
Nan Guo ◽  
Jiachen Zhao ◽  
...  
Keyword(s):  
Steady State ◽  
Dissolved Oxygen ◽  
Penicillium Chrysogenum ◽  
Large Scale ◽  
Scale Up ◽  
Redox Status ◽  
Oxygen Availability ◽  
Industrial Scale ◽  
Cell Factory ◽  
Microbial Cell Factory

Bioreactor scale-up from the laboratory scale to the industrial scale has always been a pivotal step in bioprocess development. However, the transition of a bioeconomy from innovation to commercialization is often hampered by performance loss in titer, rate and yield. These are often ascribed to temporal variations of substrate and dissolved oxygen (for instance) in the environment, experienced by microorganisms at the industrial scale. Oscillations in dissolved oxygen (DO) concentration are not uncommon. Furthermore, these fluctuations can be exacerbated with poor mixing and mass transfer limitations, especially in fermentations with filamentous fungus as the microbial cell factory. In this work, the response of glucose-limited chemostat cultures of an industrial Penicillium chrysogenum strain to different dissolved oxygen levels was assessed under both DO shift-down (60% → 20%, 10% and 5%) and DO ramp-down (60% → 0% in 24 h) conditions. Collectively, the results revealed that the penicillin productivity decreased as the DO level dropped down below 20%, while the byproducts, e.g., 6-oxopiperidine-2-carboxylic acid (OPC) and 6-aminopenicillanic acid (6APA), accumulated. Following DO ramp-down, penicillin productivity under DO shift-up experiments returned to its maximum value in 60 h when the DO was reset to 60%. The result showed that a higher cytosolic redox status, indicated by NADH/NAD+, was observed in the presence of insufficient oxygen supply. Consistent with this, flux balance analysis indicated that the flux through the glyoxylate shunt was increased by a factor of 50 at a DO value of 5% compared to the reference control, favoring the maintenance of redox status. Interestingly, it was observed that, in comparison with the reference control, the penicillin productivity was reduced by 25% at a DO value of 5% under steady state conditions. Only a 14% reduction in penicillin productivity was observed as the DO level was ramped down to 0. Furthermore, intracellular levels of amino acids were less sensitive to DO levels at DO shift-down relative to DO ramp-down conditions; this difference could be caused by different timescales between turnover rates of amino acid pools (tens of seconds to minutes) and DO switches (hours to days at steady state and minutes to hours at ramp-down). In summary, this study showed that changes in oxygen availability can lead to rapid metabolite, flux and productivity responses, and dynamic DO perturbations could provide insight into understanding of metabolic responses in large-scale bioreactors.

scholarly journals Enhanced production of taxadiene in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Behnaz Nowrouzi ◽  
Rachel Li ◽  
Laura E. Walls ◽  
Leopold d’Espaux ◽  
Koray Malci ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Shake Flask ◽  
Scale Up ◽  
Cost Effective ◽  
Cancer Drug ◽  
List Type ◽  
Taxadiene Synthase ◽  
Enhanced Production ◽  
Anti Cancer ◽  
Positive Effect

AbstractCost-effective production of the highly effective anti-cancer drug, paclitaxel (Taxol®), remains limited despite growing global demands. Low yields of the critical taxadiene precursor remains a key bottleneck in microbial production. In this study, the key challenge of poor taxadiene synthase (TASY) solubility in S. cerevisiae was revealed, and the strains were strategically engineered to relieve this bottleneck. Multi-copy chromosomal integration of TASY harbouring a selection of fusion solubility tags improved taxadiene titres 22-fold, up to 57 ± 3 mg/L at 30 °C at shake flask scale. The scalability of the process was highlighted through achieving similar titres during scale up to 25 mL and 250 mL in shake flask and bioreactor cultivations, respectively. Maximum taxadiene titres of 129 ± 15 mg/L and 119 mg/L were achieved through shake flask and bioreactor cultivation, respectively, of the optimal strain at a reduced temperature of 20 °C. The results highlight the positive effect of coupling molecular biology tools with bioprocess variable optimisation on synthetic pathway development.HighlightsMaximum taxadiene titre of 129 ± 15 mg/L in Saccharomyces cerevisiae at 20 °CIntegrating fusion protein tagged-taxadiene synthase improved taxadiene titre.Consistent taxadiene titres were achieved at the micro-and mini-bioreactor scales.

scholarly journals Specifications of Standards in Systems and Synthetic Biology

2015 ◽  
Vol 12 (2) ◽  
pp. 1-3 ◽  
Author(s):  
Falk Schreiber ◽  
Gary D. Bader ◽  
Martin Golebiewski ◽  
Michael Hucka ◽  
Benjamin Kormeier ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Information Exchange ◽  
Computational Models ◽  
Access Point ◽  
Economic Benefits ◽  
Special Issue ◽  
Community Initiative ◽  
Central Access ◽  
Oral Presentations ◽  
Modeling In Biology

Summary Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic benefits, such as making information exchange, production, and services more efficient. However, novel, innovative areas often either lack proper standards, or documents about standards in these areas are not available from a centralised platform or formal body (such as the International Standardisation Organisation).Systems and synthetic biology is a relatively novel area, and it is only in the last decade that the standardisation of data, information, and models related to systems and synthetic biology has become a community-wide effort. Several open standards have been established and are under continuous development as a community initiative. COMBINE, the ‘COmputational Modeling in BIology’ NEtwork [1] has been established as an umbrella initiative to coordinate and promote the development of the various community standards and formats for computational models. There are yearly two meeting, HARMONY (Hackathons on Resources for Modeling in Biology), Hackathon-type meetings with a focus on development of the support for standards, and COMBINE forums, workshop-style events with oral presentations, discussion, poster, and breakout sessions for further developing the standards. For more information see http://co.mbine.org/.So far the different standards were published and made accessible through the standards’ web-pages or preprint services. The aim of this special issue is to provide a single, easily accessible and citable platform for the publication of standards in systems and synthetic biology. This special issue is intended to serve as a central access point to standards and related initiatives in systems and synthetic biology, it will be published annually to provide an opportunity for standard development groups to communicate updated specifications.

scholarly journals Beyond the Core: Who Has Larger Social Networks?

Social Forces ◽  
2020 ◽  
Author(s):  
Bas Hofstra ◽  
Rense Corten ◽  
Frank van Tubergen
Keyword(s):  
Social Networks ◽  
Individual Variation ◽  
Bayesian Modeling ◽  
State Of The Art ◽  
Scale Up ◽  
Network Size ◽  
Future Research ◽  
Social Contacts ◽  
Core Networks ◽  
Social Network Size

Abstract The sociological literature on social networks overwhelmingly considers the number of core social contacts. Social networks, however, reach far beyond this small number of social ties. We know little about individual variation in the size of such extended social networks. In this study, we move beyond core networks and explain individual variation in the extended social network size among youth. We use survey data of Dutch adolescents (N = 5,921) and use two state-of-the-art measurements to compute extended network sizes: network scale-up methods through Bayesian modeling and the observed number of contacts on Facebook. Among both measurements, we find that extended networks are larger among ethnic majority members, girls, and those who often engage in social foci. This highlights a crucial role for preferences and opportunity in the genesis of extended networks. Additionally, we find that differences between both network sizes (scale-up and Facebook) are smaller for girls and higher educated. We discuss the implications of these findings and suggest directions for future research.

scholarly journals Prospects for Hermetic Sealing of Scaled-Up Photoelectrochemical Hydrogen Generators for Reliable and Risk Free Operation

Energies ◽  
2019 ◽  
Vol 12 (21) ◽  
pp. 4176 ◽  
Author(s):  
Sonya Calnan ◽  
Stefan Aschbrenner ◽  
Fuxi Bao ◽  
Erno Kemppainen ◽  
Iris Dorbandt ◽  
...  
Keyword(s):  
State Of The Art ◽  
Early Stage ◽  
Scale Up ◽  
Energy System ◽  
Future Research ◽  
Reliable Operation ◽  
Global Energy ◽  
Hermetic Sealing ◽  
Electrochemical Devices ◽  
Global Energy Supply

Photo-electrochemical (PEC) systems have the potential to contribute to de-carbonation of the global energy supply because solar energy can be directly converted to hydrogen, which can be burnt without the release of greenhouse gases. However, meaningful deployment of PEC technology in the global energy system, even when highly efficient scaled up devices become available, shall only be a reality when their safe and reliable operation can be guaranteed over several years of service life. The first part of this review discusses the importance of hermetic sealing of up scaled PEC device provided by the casing and sealing joints from a reliability and risk perspective. The second part of the review presents a survey of fully functional devices and early stage demonstrators and uses this to establish the extent to which the state of the art in PEC device design address the issue of hermetic sealing. The survey revealed that current material choices and sealing techniques are still unsuitable for scale–up and commercialization. Accordingly, we examined possible synergies with related photovoltaic and electrochemical devices that have been commericalised, and derived therefrom, recommendations for future research routes that could accelerate the development of hermetic seals of PEC devices.

scholarly journals Machine learning for digital try-on: Challenges and progress

2020 ◽  
Author(s):  
Junbang Liang ◽  
Ming C. Lin
Keyword(s):  
Machine Learning ◽  
State Of The Art ◽  
Economic Benefits ◽  
The Body ◽  
Future Directions ◽  
Recent Advances ◽  
Practical Constraints

Abstract Digital try-on systems for e-commerce have the potential to change people's lives and provide notable economic benefits. However, their development is limited by practical constraints, such as accurate sizing of the body and realism of demonstrations. We enumerate three open challenges remaining for a complete and easy-to-use try-on system that recent advances in machine learning make increasingly tractable. For each, we describe the problem, introduce state-of-the-art approaches, and provide future directions.

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