We present a framework for the efficient representation, generation, and modeling of superstructures for process synthesis. First, we develop a new representation based on three basic elements: units, ports, and conditioning streams. Second, we present four rules based on "minimal" and "feasible" component sets for the generation of simple superstructures containing all feasible embedded processes.Third, in terms of modeling, we develop a modular approach, and formulate models for each basic element. We also present a canonical form of element models using input/output variables and constrained/free variables. The proposed methods provide a coherent framework for superstructure-based process synthesis, allowing efficient model generation and modification.

Microbial conversion of renewable feedstocks to high-value chemicals is an attractive alternative to current petrochemical processes because it offers the potential to reduce net CO emissions and integrate with bioremediation objectives. Microbes have been genetically engineered to produce a growing number of high-value chemicals in sufficient titer, rate, and yield from renewable feedstocks. However, high-yield bioconversion is only one aspect of an economically viable process. Separation of biologically synthesized chemicals from process streams is a major challenge that can contribute to >70% of the total production costs. Thus, process feasibility is dependent upon the efficient selection of separation technologies. This selection is dependent on upstream processing or biological parameters, such as microbial species, product titer and yield, and localization. Our goal is to present a roadmap for selection of appropriate technologies and generation of separation schemes for efficient recovery of bio-based chemicals by utilizing information from upstream processing, separation science and commercial requirements. To achieve this, we use a separation system comprising of three stages: (I) cell and product isolation, (II) product concentration, and (III) product purification and refinement. In each stage, we review the technology alternatives available for different tasks in terms of separation principles, important operating conditions, performance parameters, advantages and disadvantages. We generate separation schemes based on product localization and its solubility in water, the two most distinguishing properties. Subsequently, we present ideas for simplification of these schemes based on additional properties, such as physical state, density, volatility, and intended use. This simplification selectively narrows down the technology options and can be used for systematic process synthesis and optimal recovery of bio-based chemicals.

BackgroundBioseparations can contribute to more than 70% in the total production cost of a bio-based chemical, and if the desired chemical is localized intracellularly, there can be additional challenges associated with its recovery. Based on the properties of the desired chemical and other components in the stream, there can be multiple feasible options for product recovery. These options are composed of several alternative technologies, performing similar tasks. The suitability of a technology for a particular chemical depends on (1) its performance parameters, such as separation efficiency; (2) cost or amount of added separating agent; (3) properties of the bioreactor effluent (e.g., biomass titer, product content); and (4) final product specifications. Our goal is to first synthesize alternative separation options and then analyze how technology selection affects the overall process economics. To achieve this, we propose an optimization-based framework that helps in identifying the critical technologies and parameters.ResultsWe study the separation networks for two representative classes of chemicals based on their properties. The separation network is divided into three stages: cell and product isolation (stage I), product concentration (II), and product purification and refining (III). Each stage exploits differences in specific product properties for achieving the desired product quality. The cost contribution analysis for the two cases (intracellular insoluble and intracellular soluble) reveals that stage I is the key cost contributor (>70% of the overall cost). Further analysis suggests that changes in input conditions and technology performance parameters lead to new designs primarily in stage I.ConclusionsThe proposed framework provides significant insights for technology selection and assists in making informed decisions regarding technologies that should be used in combination for a given set of stream/product properties and final output specifications. Additionally, the parametric sensitivity provides an opportunity to make crucial design and selection decisions in a comprehensive and rational manner. This will prove valuable in the selection of chemicals to be produced using bioconversions (bioproducts) as well as in creating better bioseparation flow sheets for detailed economic assessment and process implementation on the commercial scale.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-017-0804-2) contains supplementary material, which is available to authorized users.

BackgroundRecent advances in metabolic engineering enable the production of chemicals from sugars through microbial bio-conversion. Terpenes have attracted substantial attention due to their relatively high prices and wide applications in different industries. To this end, we synthesize and assess processes for microbial production of terpenes.ResultsTo explain a counterintuitive experimental phenomenon where terpenes such as limonene (normal boiling point 176 °C) are often found to be 100% present in the vapor phase after bio-conversion (operating at only ~ 30 °C), we first analyze the vapor–liquid equilibrium for systems containing terpenes. Then, we propose alternative production configurations, which are further studied, using limonene as an example, in several case studies. Next, we perform economic assessment of the alternative processes and identify the major cost components. Finally, we extend the assessment to account for different process parameters, terpene products, ways to address terpene toxicity (microbial engineering vs. solvent use), and cellulosic biomass as a feedstock. We identify the key cost drivers to be (1) feed glucose concentration (wt%), (2) product yield (% of maximum theoretical yield) and (3) VVM (Volume of air per Volume of broth liquid per Minute, i.e., aeration rate in min−1). The production of limonene, based on current experimental data, is found to be economically infeasible (production cost ~ 465 $/kg vs. market selling price ~ 7 $/kg), but higher glucose concentration and yield can lower the cost. Among 12 terpenes studied, limonene appears to be the most reasonable short-term target because of its large market size (~ 160 million $/year in the US) and the relatively easier to achieve break-even yield (~ 30%, assuming a 14 wt% feed glucose concentration and 0.1 min−1 VVM).ConclusionsThe methods proposed in this work are applicable to a range of terpenes as well as other extracellular insoluble chemicals with density lower than that of water, such as fatty acids. The results provide guidance for future research in metabolic engineering toward terpenes production in terms of setting targets for key design parameters.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1285-7) contains supplementary material, which is available to authorized users.

Modern biotechnologies enable the production of chemicals using engineered microorganisms. However, the cost of downstream recovery and purification steps is high, which means that the feasibility of bio-based chemicals production depends heavily on the synthesis of cost-effective separation networks. To this end, we develop a superstructure-based framework for bio-separation network synthesis. Based on general separation principles and insights obtained from industrial processes for specific products, we first identify four separation stages: cell treatment, product phase isolation, concentration and purification, and refinement. For each stage, we systematically implement a set of connectivity rules to develop stage-superstructures, all of which are then integrated to generate a general superstructure that accounts for all types of chemicals that can be produced using microorganisms. We further develop a superstructure reduction method to solve specific instances, based on product attributes, technology availability, case-specific considerations, and final product stream specifications. A general optimization model, including shortcut models for all technologies, is formulated. The proposed framework enables preliminary synthesis and analysis of bio-separation networks, and thus estimation of separation costs.

The production of chemicals from biomass has received significant attention due to its potential to reduce greenhouse gas (GHG) emissions. In this work, we develop a systematic framework to quantitatively analyze the mitigation potential of 25 large-volume and promising platform biochemicals. To properly account for the energy requirements of producing different biochemicals, we construct material and energy balances of the biorefinery and develop simulation and optimization models to calculate the energy needed to separate and purify these biochemicals. We show that biomass-based production can lead to significant GHG mitigation. Notably, 24 out of the 25 biochemicals have lower GHG emissions compared to their fossil-fuel-derived counterparts. Under the most conservative assumptions (i.e., 25% conversion and high separation energy), biochemicals can reduce GHG emissions by up to 88%. Under the most optimistic assumptions (i.e., 75% conversion and easy separation), the emission reductions can be as great as 94%. Finally, we discuss constraints on the fraction of chemicals that can be replaced due to biomass availability limitations and identify molecular characteristics that can be used for the prioritization of chemicals to be produced from biomass.

Recent progress in metabolic engineering and synthetic biology enables the use of microorganisms for the production of chemicals-"bio-based chemicals." However, it is still unclear which chemicals have the highest economic prospect. To this end, we develop a framework for the identification of such promising ones. Specifically, we first develop a genome-scale constraint-based metabolic modeling approach, which is used to identify a candidate pool of 209 chemicals (together with the estimated yield, productivity, and residence time for each) from the intersection of the high-production-volume chemicals and the KEGG and MetaCyc databases. Second, we design three screening criteria based on a chemical's profit margin, market volume, and market size. The total process cost, including the downstream separation cost, is systematically incorporated into the evaluation. Third, given the three aforementioned criteria, we identify 32 products as economically promising if the maximum yields can be achieved, and 22 products if the maximum productivities can be achieved. The breakeven titer that renders zero profit margin for each product is also presented. Comparisons between extracellular and intracellular production, as well as Escherichia coli and Saccharomyces cerevisiae systems are also discussed. The proposed framework provides important guidance for future studies in the production of bio-based chemicals. It is also flexible in that the databases, yield estimations, and criteria can be modified to customize the screening.

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