Development and monitoring of an integrated bioprocess for production of a potential malaria vaccine with Pichia pastoris

An engineered variant of the yeast Pichia pastoris was used to produce the potential malaria vaccine D1M1. This paper describes the implementation of an expanded bed adsorption chromatography step into a sequential cultivation process of the yeast in order to link protein expression, cell release, and product capture of the secreted protein in a fully automated plant. The process is operated with a semi-continuous strategy for an integrated production. Process improvements have been achieved using design of experiments. Resulting purities of product achieved up to 87% with recoveries of 51% in a single downstream operation. Furthermore, a multivariate analysis of historical batch data was used to develop a golden batch model for process monitoring.     

Malic acid production from renewables: a review

Malic acid derived from fossil resources is currently applied in the food and beverage industries with a medium global production capacity. However, in the transition from a fossil-based to a bio-based economy, biotechnologically produced l -malic acid may become an important platform chemical with many new applications, especially in the field of biopolymers. In this review, currently used petrochemical production routes to dl -malic acid are outlined and insights into possible bio-based alternatives for microbial l -malic acid production are provided. Besides ecological reasons, the possibility to produce enantiopure l -malic acid by microbial fermentation is the biggest advantage over chemical synthesis. State-of-the-art and open challenges concerning production host engineering, substrate choice and downstream processing are addressed. With regard to production hosts, a literature overview is given covering the leading natural production strains of Aspergillus, Ustilago and Aureobasidium, as well as Escherichia coli as the most important engineered recombinant host. The utilization of renewable substrates as an alternative to glucose is emphasized in particular as a key aspect for a competitive bio-based production. Out of the alternative substrates discussed in this review, the industrial side-streams crude glycerol and molasses seem to be most promising for large-scale l -malic acid production. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Nonlinear control of the dissolved oxygen concentration integrated with a biomass estimator for production of Bacillus thuringiensis δ-endotoxins

Bacillus thuringiensis is a microorganism that allows the biosynthesis of δ-endotoxins with toxic properties against some insect larvae, being often used for the production of biological insecticides. A key issue for the bioprocess design consists in adequately tracking a pre-specified optimal profile of the dissolved oxygen concentration. To this effect, this paper aims at developing a novel control law based on a nonlinear dynamic inversion method. The closed-loop strategy includes an observer based on a Bayesian Regression with Gaussian Process, which is used for on-line estimating the biomass present in the bioreactor. Unlike other approaches, the proposed controller leads to an improved response time with effective disturbance rejection properties, while simultaneously prevents undesired oscillations of the dissolved oxygen concentration. Simulation results based on available experimental data were used to show the effectiveness of the proposal.     

Performance evaluation of an ANN–GA aided experimental modeling and optimization procedure for enhanced synthesis of marine biosurfactant in a stirred tank reactor

BACKGROUND: An improved resilient back‐propagation neural network modeling coupled with genetic algorithm aided optimization technique was employed for optimizing the process variables to maximize lipopeptide biosurfactant production by marine Bacillus circulans. RESULTS: An artificial neural network (ANN) was used to develop a non‐linear model based on a 2⁴ full factorial central composite design involving four independent parameters, agitation, aeration, temperature and pH with biosurfactant concentration as the process output. The polynomial model was optimized to maximize lipopeptide biosurfactants concentration using a genetic algorithm (GA). The ranges and levels of these critical process parameters were determined through single‐factor‐at‐a‐time experimental strategy. Improved ANN‐GA modeling and optimization were performed using MATLAB v.7.6 and the experimental design was obtained using Design Expert v.7.0. The ANN model was developed using the advanced neural network architecture called resilient back‐propagation algorithm. CONCLUSION: Process optimization for maximum production of marine microbial surfactant involving ANN‐GA aided experimental modeling and optimization was successfully carried out as the predicted optimal conditions were well validated by performing actual fermentation experiments. Approximately 52% enhancement in biosurfactant concentration was achieved using the above‐mentioned optimization strategy. © 2012 Society of Chemical Industry     

An approach to mechanistic event recognition applied on monitoring organic matter depletion in SBRs

A fundamental practice in process engineering is monitoring the state dynamics of a system. Unfortunately, observability of some states is related to high costs, time, and efforts. The mechanistic event recognition (MER) aims to detect an event (defined as a change of the system with specific significance to the operation of the process) that cannot be directly observed but has some predictable effect on the dynamics of the systems. MER attempts to apply fault diagnosis techniques using mechanistic “recognition” models to describe the process. A systematic method for building recognition models using optimal experimental design tools is presented. As proof of concept, the MER approach to detect organic matter depletion in sequencing batch reactors, measuring only ammonia, dissolved oxygen, and nitroxides is applied. The event, that is, consumption of organic matter to a level below 50 gCOD/m³, was successfully detected even though microbial activity is known to continue after organic matter depletion. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3460–3472, 2014     

7-氨基去乙酰氧基头孢烷酸生产工艺研究进展

介绍了 7 氨基去乙酰氧基头孢烷酸化学法合成工艺 ,综述了酶法和发酵法合成7 ADCA的研究现状。生物法合成经济且环境友好 ,是工业中合成 7 ADCA的发展方向     

固相反硝化在水污染治理中的研究进展

水环境中硝酸盐污染是普遍存在的问题。固相反硝化（SPD）技术由于其相对于水基反硝化在水修复中的显著优势而受到越来越多的关注。本文对SPD在水修复中的应用提出了新的看法,介绍了SPD中氮转化的过程和机理,如直接反硝化、异化硝酸盐还原成铵和厌氧氨氧化;讨论了碳底物在SPD中转化的主要过程;研究了SPD的主要局限性,包括碳源可用性低,NO₂^-和N₂O积累,溶解有机碳释放和NH₄⁺的生产,并总结了相关的限制因素;此外,还介绍了一些新的措施来减轻这些限制,如应用可生物降解的聚合物底物和异养自养反硝化HAD过程;最后讨论了同时去除硝酸盐和一些典型污染物以扩大SPD应用的方法。本综述试图提高人们对废水处理或水修复工程中反硝化过程的理解。     

去除废水中顽固污染物:染料废水脱色和生物降解的联合处理过程(英文)

While conventional wastewater treatments for urban effluents are fairly routine and have proved highly effective,industrial wastewater requires more complex and specific treatments.This paper provides a technological strategy for removal of recalcitrant contaminants based on a hybrid treatment system.The model effluent containing a binary mixture of synthetic dyes is treated by a combination of a preliminary physicochemical stage followed by a biological stage based on ligninolytic enzymes produced by Phanerochaete chrysosporium.This proposal includes biosorption onto peat as pretreatment,which decreases the volume and concentration to be treated in the biological reactor,thereby obtaining a completely decolorized effluent.The treated wastewater can therefore be reused in the dyeing baths with the consequent saving of water resources.