Biotechnology and Bioengineering最新文献

Recombinant protein expression in heterologous biological systems is an expanding field in synthetic biology. Photosynthetic organisms have the potential to provide an efficient low-cost platform for recombinant protein production because they require minimal growth nutrients and are less susceptible to zoonotic and other contaminants. Cyanobacteria are a class of microorganisms that are gaining as the preferred photosynthetic cell factories for product generation. In this study, the cyanobacterium Synechocystis sp. PCC 6803 was used as a host to stably over-express a functional form of the human interferon α−2 (IFN), as a fusion construct with the abundant CpcB β-subunit of phycocyanin. To cleave and isolate the free form of IFN from the fusion protein, different constructs were designed containing the Tobacco Etch Virus (TEV) or Human Rhinovirus (hrv) 3 C protease cleaving loci, placed between the leading CpcB and trailing IFN moieties of the fusion proteins. The work examined the comparative cleaving efficacy of TEV and HRV proteases in separating IFN from such over-expressed phycocyanin fusion protein complexes. It was concluded that the HRV protease system is superior to that of TEV, and that of other cleaving proteases recently tested, and may thus be incorporated in the toolkit of cyanobacterial synthetic biology for recombinant protein synthesis and isolation.

The development of autonomous agents in bioprocess development is crucial for advancing biopharma innovation. Time and resources required to develop and transfer a process for clinical material generation can be significantly decreased. While robotics and machine learning have greatly accelerated drug discovery and initial screening, the later stages of development have primarily benefited from experimental automation, lacking advanced computational tools for experimental planning and execution. For example, in the development of new monoclonal antibodies, the search for optimal upstream conditions (such as feeding strategy, pH, temperature, and media composition) is often conducted using sophisticated high-throughput (HT) mini-bioreactor systems, while the integration of machine learning tools for experimental design and operation in these systems have not matured accordingly. In this work, we developed an integrated user-friendly software framework that combines a Bayesian experimental design (BED) algorithm and a cognitive digital twin of the cultivation system. This framework is digitally linked to an advanced 24-parallel mini-bioreactor perfusion platform. This results in an autonomous experimental machine capable of: (1) embedding existing process knowledge, (2) learning during experimentation, (3) utilizing information from similar processes, (4) predicting future events, and (5) autonomously operating the parallel bioreactors to achieve challenging objectives. As proof of concept, we present experimental results from a 27 day-long cultivation including 20-days operated by the autonomous software agent, which successfully achieved challenging goals such as increasing the viable cell volume (VCV) and maximizing the viability throughout the experiment.

Andaluz, A., Monteverde, B., Vera, K., Tse, B., Gajic, I., Froelich, C. and Motevalian, S.P. (2025), Accelerated Adeno Associated Virus Upstream Process Development From High-Throughput Systems to Clinical Scale. Biotechnology and Bioengineering, 122: 3051-3060. https://doi.org/10.1002/bit.70052

In the originally published article, author Clifford Froelich's name was misspelled as Forelich. This has been corrected in the online version of the article.

We apologize for this error.

Microalgae offer a promising pathway for sustainable biofuel and bioproduct development, but outdoor cultivation is highly sensitive to environmental variability. To address this, the authors present an experimental monthly biomass forecasting system designed to guide operational decisions such as strain selection and pond water depth. Using the Biomass Assessment Tool (BAT) coupled with two forecasting approaches, a climatology-based method using data from Phase 2 of the North American Land Data Assimilation System (NLDAS-2) and three models from the North American Multi-Model Ensemble (NMME), the authors evaluated biomass production strategies for two high-performing algal strains (Picochlorum celeri and Tetraselmis striata) across four pond depths (15–30 cm) from 2020 to 2024 in Arizona. One of the NMME models achieved the highest selection accuracy, correctly identifying the optimal strain and pond depth in 84% of the months, with model accuracies across the NMME suite ranging from 74% to 84%. In comparison, the NLDAS-2 climatology-based approach achieved a 78% accuracy. Strain selection was consistently more accurate than pond depth selection across all methods, with one NMME model and the NMME multi-model ensemble achieving up to 92% accuracy in strain prediction. Simulation results show that forecast-informed approaches increased average biomass yields by 15% over the current State-of-Technology strategy, with gains exceeding 40% in certain months. These results highlight the potential of forecast-guided strategies to enhance biomass production and enable more adaptive, weather-resilient microalgae cultivation. The system is scalable to additional strains and geographic regions, offering a flexible tool for advancing sustainable algal production under increasingly variable environmental conditions.

RETRACTION: M. Chow-shi-yée, M. Grondin, D. A. Averill-Bates, and F. Ouellet, “Plant Protein 2-Cys Peroxiredoxin TaBAS1 Alleviates Oxidative and Nitrosative Stresses Incurred During Cryopreservation of Mammalian Cells,” Biotechnology and Bioengineering 113, no. 7 (2016): 1511-1521, https://doi.org/10.1002/bit.25921.

The above article, published online on 1 January 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Douglas S. Clark; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, Figure 4A was found to contain repetitive elements (i.e., cells) suggesting inappropriate image processing. Investigation by the publisher has confirmed the validity of the concerns.

The authors were unable to retrieve the raw data underlying Figure 4A due to the time elapsed since original publication. They also stated that the images presented in Figure 4A were acquired as original images and have not been altered in any form. The authors conducted an independent analysis of the magnified published images, highlighting that the cells identified as duplicated exhibit differences. According to the authors, the observed similarities are characteristic of cells within a homogeneous population (i.e., hepatocytes) and are therefore to be expected, thereby refuting allegations of inappropriate image editing.

However, the editors have deemed the clarification from the authors as insufficient to resolve their concerns. The similarities detected in Figure 4A were found to outweigh the differences highlighted by the authors and were considered unlikely to result solely from morphological resemblance within a homogeneous population of primary isolated hepatocytes. The editors have determined that the new experimental data generated by the authors to replace the images in Figure 4A were unsuitable for direct comparison with the originally published data, due to the substantial time gap between the two experimental sets. Therefore, the concerns of the editors were not addressed acceptably and accordingly, the article must be retracted. The authors disagree with the retraction decision.

RETRACTION: M. Grondin, F. Hamel, D. A. Averill-Bates, and F. Sarhan, “Wheat Proteins Improve Cryopreservation of Rat Hepatocytes,” Biotechnology and Bioengineering 103, no. 3 (2009): 582-591, https://doi.org/10.1002/bit.22270.

The above article, published online on 20 January 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Douglas S. Clark; and Wiley Periodicals, LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, several micrographs presented in Figure 4 were found to contain numerous repetitive elements (i.e., cells) suggesting inappropriate image processing. Furthermore, data presented in Figure 4 and part of the data presented in Figure 1 were found to have been previously published by the same author group [Grondin et al, (2009); https://doi.org/10.3727/096368909788237104]. Investigation by the publisher has confirmed the validity of the concerns.

The authors were unable to retrieve the raw data underlying Figure 4 due to the time elapsed since original publication. They also stated that the images presented in Figure 4 were acquired as original images and have not been altered in any form. They conducted an independent analysis of the magnified published images, highlighting that the cells identified as duplicated exhibit differences. According to the authors, the observed similarities are characteristic of cells within a homogeneous population (i.e., hepatocytes) and are therefore to be expected, thereby refuting allegations of inappropriate image editing. With respect to the duplication of previously published data in Figure 1 and Figure 4, the authors stated that this was due to an honest oversight because of the concurrent publication of the two studies. The authors stated that the issues identified do not affect the conclusions of the article.

However, the editors have deemed the clarification from the authors as insufficient to resolve their concerns. The similarities detected in Figure 4 were found to outweigh the differences highlighted by the authors and were considered unlikely to result solely from morphological resemblance within a homogeneous population of primary isolated hepatocytes. The editors have determined that the new experimental data generated by the authors to replace the images in Figure 4 were unsuitable for direct comparison with the originally published data, due to the substantial time gap between the two experimental sets. Therefore, the concerns of the editors were not addressed acceptably and accordingly, the article must be retracted. The authors disagree with the retraction decision.