gcFront: a tool for determining a Pareto front of growth-coupled cell factory designs

Motivation: A widely applicable strategy for developing evolutionarily robust cell factories is to knock out (KO) genes or reactions to couple chemical synthesis with cell growth. Genome-scale metabolic models enable their rational design, but KOs that provide growth-coupling (gc) are rare in the immense design space, making searching difficult and slow, and though several measures determine the utility of those strains, few drive the search. Results: To address these issues we developed a software tool named gcFront - using a genetic algorithm it explores KOs that maximise key performance objectives: cell growth, product synthesis, and coupling strength. Our measure of coupling strength facilitates the search, so gcFront not only finds a gc-design in minutes but also outputs many alternative Pareto optimal gc-designs from a single run - granting users freedom to select designs to take to the lab.

Recent Advances in the Physicochemical Properties and Biotechnological Application of Vitreoscilla Hemoglobin

Vitreoscilla hemoglobin (VHb), the first discovered bacterial hemoglobin, is a soluble heme-binding protein with a faster rate of oxygen dissociation. Since it can enhance cell growth, product synthesis and stress tolerance, VHb has been widely applied in the field of metabolic engineering for microorganisms, plants, and animals. Especially under oxygen-limited conditions, VHb can interact with terminal oxidase to deliver enough oxygen to achieve high-cell-density fermentation. In recent years, with the development of bioinformatics and synthetic biology, several novel physicochemical properties and metabolic regulatory effects of VHb have been discovered and numerous strategies have been utilized to enhance the expression level of VHb in various hosts, which greatly promotes its applications in biotechnology. Thus, in this review, the new information regarding structure, function and expressional tactics for VHb is summarized to understand its latest applications and pave a new way for the future improvement of biosynthesis for other products.

Model analysis and simulation on impacts of COVID-19 pandemic on the economy: a case study of Thailand’s GDP and its lock down measures

COVID-19 could affect the global and local economy mainly by directly affecting production, by creation of disruption in supply chains and markets, as well as through its financial impact on firms and markets and organizations. However, the extent to which the impact is felt depends a great deal on the how governments and the public react to the disease. Here, a model is proposed to investigate the effect of the spread of corona virus infection and the consequent measures taken in response to its spread to lessen its impacts on the society and the economy. The interaction between the number of infected individuals and the variations in the national Growth Product, GDP, is modeled by a system of impulsive non-linear difference equations with delays. We are specifically interested in how different lock down measures effect business recovery as reflected by the national GDP. The model is analyzed to obtain valuable insights as to the factors that could yield different successes in the pandemic control and business recovery in various scenarios. Based on data of newly infected cases and cumulative cases weekly in Thailand, the model is simulated in a variety of scenarios to illustrate how different strategies and lockdown measures may give rise to different recovery rates.

BRIDELIA SCANDENS WILD. A NEW SOURCE FOR PODOPHYLLOTOXIN PRODUCTION IN VITRO BY FEEDING CONIFERYL ALCOHOL

Objective: In the present study, a new method for the production of anticancerous compound podophyllotoxin (PTOX) was developed for Bridelia scandens Wild. by feeding coniferyl alcohol. Methods: The production of anticancerous compound PTOX through leaf explant derived calli of B. scandens. Murashige and Skoog (MS) medium fortified with 0.5 mg/l 6-Benzylaminopurine (BAP) and 0.5 mg/l 2,4-D (2,4-Dichlorophenoxyacetic acid) induced luxuriant mass of callus growth. Suspension culture was initiated by sterile MS media fortified with 0.1–1.0 mg/l BAP and 0.1–1.0 mg/l 2,4-D. and growth product was analyzed by the high-pressure liquid chromatography method. Results: Phytochemical analysis of the B. scandens leaf and leaf calli showed the presence of PTOX at the concentrations of 0.69 and 1.81, respectively. The callus cell suspension was established with the same callogenic media also it is augmented with 10–70 mg/l of coniferyl alcohol to elicit the biosynthesis of PTOX. Successive cultures of the calli suspension yielded stable production of PTOX of 3.91 mg/g dry cell weight at 50 mg/l coniferyl alcohol in the media. The biosynthesis of PTOX was ideal when plant cells were cultivated in the dark with an agitation speed of 100 rpm. Conclusion: The growth and production of PTOX were found to be better with glucose than with sucrose as the medium carbon source. The harvesting of the secondary metabolite from the in vitro grown leaf calli of B. scandens is a better way to stop the exploitation of medicinal plants.

Market Power, Growth, and Inclusion

Before the pandemic, the South African economy remained stuck in low gear, with anemic growth, stagnant private investment, and a shrinking tradable sector. Subdued growth has raised unemployment, poverty, and inequality, hindering inclusion efforts. The pandemic has worsened economic and social vulnerabilities. Economic recovery and social inclusion hinge critically on structural reforms to boost competiveness and growth. Product markets represent a cornerstone of the reform strategy. Firms have used their market power to drive up prices and limit competition. Important state-owned monopolies provide low-quality services, while representing a fiscal drag. Existing regulations inhibit the entry of both domestic and foreign firms. Addressing product markets constraints could boost per capita growth by 1 percentage point—adding about 2½ percentage points to headline growth—and foster greater inclusion.

Effect of Cysteine, Yeast Extract, pH Regulation and Gas Flow on Acetate and Ethanol Formation and Growth Profiles of Clostridium ljungdahlii Syngas Fermentation

ABSTRACTThe fermentation of synthesis gas, or syngas, which consists mainly of CO, CO2 and H2 by acetogenic bacteria has the potential to help in transitioning from a fossil-fuel-based to a renewable bio-economy. Clostridium ljungdahlii, one of such microorganisms, has as main fermentation products acetate and ethanol. Multiple research efforts have been directed towards understanding how the metabolism and the product formation of this, and other acetogenic bacteria, can be directed towards increasing productivities and yields; nonetheless, transferring those findings to a particular set-up can prove challenging. This study used a well-established and robust fed-batch fermentation system with C. ljungdahlii to look into the effects of different fermentation pH profiles, gas flow, and the supplementation with additional yeast extract or cysteine on growth, product formation ratios, yields, and productivities, as well as gas consumption. Neither yeast extract nor cysteine supplementation had a noticeable impact on cell growth, product formation or overall gas consumption. The lowering of the pH proved mainly detrimental, with decreased productivities and no improvement in ethanol ratios. The most notable shift towards ethanol was achieved by the combination of lowering both the pH and the gas flow after 24 h, but with the caveat of lower productivity. The obtained results, unexpected to some extent, highlight the necessity for a better understanding of the physiology and the metabolic regulation of acetogenic bacteria in order for this process to become more industrially relevant.

PERILAKU MENCARI PEMBIAYAAN USAHA KECIL DAN MENENGAH: SEBUAH ANALISIS ISI TERHADAP ARTIKEL XIANG & WORTHINGTON (2015) DAN SAEED & SAMEER (2015)

Currently, there are relatively few studies that have examined the comparison between the finance-seeking behavior for small and medium-sized enterprises in developed and developing countries. In general, this study aims to analyze differences in finance-seeking behavior between enterprises from Australia and Pakistan, including identifying various antecedents of finance-seeking behavior by enterprises in both countries. For this reason, we conducted an exploratory study through a content analysis of two scientific journal articles. Specifically, we systematically examine two scientific journal articles that discuss access to finance by small and medium-sized enterprises, both in terms of substance and methods. The first article was written by Xiang and Worthington and the second article was written by Saeed and Sameer. We found that the study of Xiang and Worthington succeeded in identifying various antecedents of finance-seeking behavior at the micro (internal) level, such as business objectives, profitability, growth, product and service quality, business ownership, business size, business life, and government assistance. On the other hand, the study of Saeed and Sameer revealed that there were other antecedents at the meso level (external or industrial) that could influence the search for enterprise financing, namely the concentration of the banking industry. In conclusion, the study of Saeed and Sameer further complements the study of Xiang and Worthington in identifying various antecedents of finance-seeking behavior. Saat ini ada beberapa studi yang meneliti perbandingan antara perilaku pencarian keuangan untuk usaha kecil dan menengah di negara maju dan berkembang. Secara umum, penelitian ini bertujuan untuk menganalisis perbedaan perilaku pencarian keuangan antara perusahaan dari Australia dan Pakistan, termasuk mengidentifikasi berbagai anteseden perilaku pencarian keuangan oleh perusahaan di kedua negara. Untuk alasan ini, kami melakukan studi eksplorasi melalui analisis konten dari dua artikel jurnal ilmiah. Secara khusus, kami secara sistematis memeriksa dua artikel jurnal ilmiah yang membahas akses ke keuangan oleh perusahaan kecil dan menengah, baik dari aspek substansi maupun metode. Artikel pertama ditulis oleh Xiang dan Worthington (2015) dan artikel kedua ditulis oleh Saeed dan Sameer (2015). Kami menemukan bahwa penelitian Xiang dan Worthington berhasil mengidentifikasi berbagai anteseden perilaku pencarian keuangan di tingkat mikro (internal), seperti tujuan bisnis, profitabilitas, pertumbuhan, kualitas produk dan layanan, kepemilikan bisnis, ukuran bisnis, kehidupan bisnis, dan bantuan pemerintah. Di sisi lain, studi Saeed dan Sameer mengungkapkan bahwa ada anteseden (penentu) lain di tingkat meso (eksternal atau industri) yang dapat mempengaruhi pencarian pembiayaan perusahaan, yaitu konsentrasi industri perbankan. Sebagai kesimpulan, studi Saeed dan Sameer lebih lanjut melengkapi studi tentang Xiang dan Worthington dalam mengidentifikasi berbagai anteseden perilaku pencarian keuangan.

Alkane and wax ester production from lignin derived molecules

Lignin has potential as a sustainable feedstock for microbial production of industrially relevant molecules. However, the required lignin depolymerization yields a heterogenic mixture of aromatic monomers that are challenging substrates for the microorganisms commonly used in industry. Here, we investigated the properties of lignin-derived molecules (LDMs), namely coumarate, ferulate, and caffeate, in the synthesis of biomass and products in a LDM-utilizing bacterial hostAcinetobacter baylyiADP1. The biosynthesis products, wax esters and alkanes, are relevant compounds for the chemical and fuel industries. InA. baylyiADP1, wax esters are produced by a native pathway, whereas alkanes are produced by a synthetic pathway introduced to the host. Using individual LDMs as substrates, the growth, product formation, and toxicity to cells were monitored with internal biosensors. Of the tested LDMs, coumarate was the most propitious in terms of product synthesis. Wax esters were produced from coumarate with a yield and titer of 40 mg /gcoumarateand 221 mg/L, whereas alkanes were produced with a yield of 62.3 μg /gcoumarateand titer of 152 μg/L. This study demonstrates the microbial preference for certain LDMs, and highlights the potential ofA. baylyiADP1 as a convenient host for LDM upgrading to value-added products.

Analyte Tracking for Novel Bio-Applications

Modern cell culture as well as sophisticated bio-applications involve complex biochemical processes, which are required to induce growth, product development or material degradation. Tracking the reaction processes inside the application presents a major challenge due to its complexity. The development of new analysis and tracking mechanisms for such application presents a solution to fully understand the process. In addition, the applied sensors are required to monitor the reactions enable a live tracking of the process. Furthermore, this gives the opportunity to influence and manipulate reactions to further enhance the application of the process. Possible analytes for tracking during processes can be chemical origin such as glucose, cytokines, antibiotics and growth factors, which are included in the culture medium. Based on the complexity of the culture or bio-application the sensor tracking mechanism has to be adapted to ensure full process control. A variety of different approaches can be used for the tracking mechanism.