Stephen S Fong

Stephen S Fong
Virginia Commonwealth University | VCU · Chemical and Life Science Engineering

Ph.D.

About

120
Publications
19,616
Reads
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4,185
Citations
Citations since 2017
27 Research Items
2230 Citations
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20172018201920202021202220230100200300400
20172018201920202021202220230100200300400
20172018201920202021202220230100200300400
Additional affiliations
August 2005 - present
Virginia Commonwealth University
August 1998 - July 2005
University of California, San Diego
August 1998 - June 2004
University of California, San Diego
Position
  • PhD Student

Publications

Publications (120)
Article
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Air pollution and the urban heat island effect are consistently linked to numerous respiratory and heat-related illnesses. Additionally, these stressors disproportionately impact low-income and historically marginalized communities due to their proximity to emissions sources, lack of access to green space, and exposure to other adverse environmenta...
Article
Genome-scale metabolic modeling is a scalable and extensible computational method for analyzing and predicting biological function. With the ongoing improvements in computational methods and experimental capabilities, genome-scale metabolic models (GEMs) are demonstrating utility in addressing human health applications. The initial areas of highest...
Article
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The impact of microorganisms on human health has long been acknowledged and studied, but recent advances in research methodologies have enabled a new systems-level perspective on the collections of microorganisms associated with humans, the human microbiome. Large-scale collaborative efforts such as the NIH Human Microbiome Project have sought to k...
Article
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Research that meaningfully integrates constraint-based modeling with machine learning is at its infancy but holds much promise. Here, we consider where machine learning has been implemented within the constraint-based modeling reconstruction framework and highlight the need to develop approaches that can identify meaningful features from large-scal...
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The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes ‘omics’ data from approximatel...
Article
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The microbiome of the female reproductive tract has implications for women’s reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or...
Article
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Background Serratia marcescens is a chitinolytic bacterium that can potentially be used for consolidated bioprocessing to convert chitin to value-added chemicals. Currently, S. marcescens is poorly characterized and studies on intracellular metabolic and regulatory mechanisms would expedite development of bioprocessing applications. Results In thi...
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During microbial applications, metabolic burdens can lead to a significant drop in cell performance. Novel synthetic biology tools or multi-step bioprocessing (e.g., fermentation followed by chemical conversions) are therefore needed to avoid compromised biochemical productivity from over-burdened cells. A possible solution to address metabolic bur...
Article
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Being capable of hydrolyzing chitin, chitinases have various applications such as production of N-acetylchitooligosaccharides (COSs) and N-acetylglucosamine (GlcNAc), degrading chitin as a consolidated bioprocessing, and bio-control of fungal phytopathogens. Here, a putative chitinase in Thermobifida fusca, Tfu_0580, is characterized. Tfu_0580 was...
Article
The photoelectrochemical electrode has been intensively studied in recent years as a means of generating electricity from light through the use of intact thylakoid membranes or highly purified photosystem II. PSII-enriched thylakoid membrane fragments (PSII-BBY), also have the potential to construct the photoelectrochemical anode. In this study, we...
Article
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Chitin is an abundant, biorenewable, nitrogen‐rich biomass feedstock that can be potentially developed for biochemical production, however, efficient bioprocesses have yet to be established. Here, we demonstrate an engineered bioprocess to produce N‐acetylneuraminic acid (Neu5Ac) directly from chitin using the chitinolytic bacterium, Serratia marce...
Article
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Actinomycetes have a long history of being the source of numerous valuable natural products and medicinals. To expedite product discovery and optimization of biochemical production, high-throughput technologies can now be used to screen the library of compounds present (or produced) at a given time in an organism. This not only facilitates chemical...
Article
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Background: UP elements (upstream element) are DNA sequences upstream of a promoter that interact with the α-subunit of RNA polymerase (RNAP) and can affect transcription by altering the binding RNAP to DNA. However, details of UP element and binding affinity effects on transcriptional strength are unclear. Results: Here, we investigated the effect...
Article
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Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly uti...
Article
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Microbial utilization of chitin, a potential renewable biomass feedstock, is being pursued as a means of developing novel consolidated bioprocessing for the production of chemicals. Serratia marcescens is a Gram-negative bacterium that is known for its chitinolytic capability and as a native 2,3-butanediol producer. In S. marcescens, ChiR has been...
Article
We introduce a framework for finding and analyzing all optimal solutions to a linear-programming-based model for cellular metabolism. The implementation of a pivoting-based method for generating alternate optimal reaction fluxes is described. We present a novel strongly polynomial algorithm to decompose a matrix of alternate optimal solutions of an...
Chapter
This chapter focuses on the utilization of biomass for ethanol production. The characteristics of biomass are introduced as well as the main sources of biomass. Following that, the different pretreatment methods that have been investigated to date will be explored to understand the pretreatment goals as well as evaluate the methods for potential in...
Article
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Direct, untargeted sequencing of environmental samples (metagenomics) and de novo genome assembly enable the study of uncultured and phylogenetically divergent organisms. However, separating individual genomes from a mixed community has often relied on the differential-coverage analysis of multiple, deeply sequenced samples. In the metagenomic inve...
Chapter
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With the advent of synthetic biology, it is possible to accelerate metabolic engineering research due to lower cost gene synthesis. In particular, genetically encoded biosensors can be used in synthetic circuits to dynamically respond to metabolites to actuate desired metabolic engineering functions. Biosensors can be employed to target high-produc...
Article
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Importance: The bryostatins are potent protein kinase C activators that have been evaluated in clinical trials for a number of indications, including cancer and Alzheimer's disease. There is, therefore, considerable interest in securing a renewable supply of these compounds, which is currently only possible through aquaculture of Bugula neritina a...
Article
Engineering cell metabolism for bioproduction not only consumes building blocks and energy molecules (e.g., ATP) but also triggers energetic inefficiency inside the cell. The metabolic burdens on microbial workhorses lead to undesirable physiological changes, placing hidden constraints on host productivity. We discuss cell physiological responses t...
Article
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Constraint‐based analysis of genome‐scale models (GEMs) arose shortly after the first genome sequences became available. As numerous reviews of the field show, this approach and methodology has proven to be successful in studying a wide range of biological phenomena (McCloskey et al, 2013; Bordbar et al, 2014). However, efforts to expand the user b...
Article
Thermobifida fusca is a moderately thermophilic actinobacterium naturally capable of utilizing lignocellulosic biomass. The B6 strain of T. fusca was previously engineered to produce 1-propanol directly on lignocellulosic biomass by expressing a bifunctional butyraldehyde/alcohol dehydrogenase (adhE2). To characterize the intracellular mechanisms r...
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Recent advances in experimental and computational synthetic biology are extremely useful for achieving metabolic engineering objectives. The integration of synthetic biology and metabolic engineering within an iterative design-build-test framework will improve the practice of metabolic engineering by relying more on efficient design strategies. Com...
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Thermoanaerobacterium saccharolyticum is a hemicellulose-degrading thermophilic anaerobe that was previously engineered to produce ethanol at high yield. A major project was undertaken to develop this organism into an industrial biocatalyst, but the lack of genome information and resources were recognized early on as a key limitation. Here we prese...
Article
Biosynthetic pathways that make secondary metabolites are widespread amongst bacteria, and the resulting small molecules presumably confer a selective advantage to producers. Because bacteria live in complex mixed communities in the environment and in association with higher host organisms, a variety of functions have been suggested for secondary m...
Article
With the increasing availability of deeply sequenced data sets, it has become clear that the biosynthetic potential of uncultured microbes, which are believed to account for 99.9% of bacteria, remains largely untapped. Understanding the ecological roles and full biotechnological potential of these uncultivated microbes has historically been limited...
Article
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Concurrent advances in a number of fields have fostered the development of bioprocesses for biochemical production. Ideally, future bioprocesses will meet the demands of commercial chemical markets in an economical fashion while being sustainable through the use of renewable starting materials. A number of different renewable and abundant biopolyme...
Article
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Lignocellulose, which comprises the cell walls of plants, is the Earth’s most abundant renewable source of convertible biomass. However, in order to access the fermentable sugars of the cellulose and hemicellulose fraction, the extremely recalcitrant lignin heteropolymer must be hydrolyzed and removed—usually by harsh, costly thermochemical pretrea...
Article
The genome-scale metabolic flux modeling of anaerobic metabolism relevant to biotechnology has recently expanded in focus. In particular, there is interest in modeling facultative anaerobes (including yeast) to learn how to effectively eliminate microaerobic environments in favor of anaerobiosis. This is advantageous to bioprocessing and maximizes...
Article
Thermobifida fusca not only produces cellulases, hemicellulases and xylanases, but also excretes butyric acid. In order to achieve a high yield of butyric acid, the effect of different carbon sources: mannose, xylose, lactose, cellobiose, glucose, sucrose and acetates, on butyric acid production was studied. The highest yield of butyric acid was 0.6...
Article
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Background Thermobifida fusca is a cellulolytic bacterium with potential to be used as a platform organism for sustainable industrial production of biofuels, pharmaceutical ingredients and other bioprocesses due to its capability of potential to convert plant biomass to value-added chemicals. To best develop T. fusca as a bioprocess organism, it is...
Article
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Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools have enabled different approaches to metabolic engineering. One app...
Article
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Experimental techniques allow engineering of biological systems to modify functionality; however, there still remains a need to develop tools to prioritize targets for modification. In this study, agent-based modeling (ABM) was used to build stochastic models of complexed and non-complexed cellulose hydrolysis, including enzymatic mechanisms for en...
Conference Paper
DNA synthesis gives biologists and engineers the ability to program microorganisms by genetically encoding specific functionality. Although de novo DNA synthesis provides a high level of designability, its application in biology and biotechnology is currently limited due to its cost. The cost of synthesis does not scale linearly with sequence lengt...
Article
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Even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid, and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. Advances in cloning techniques have resulted in powerful in vitro and in vivo assembly of DNA. However, monetary and time costs have limited these approaches. Here...
Article
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Genome-scale reconstructions are often used for studying relationships between fundamental components of a metabolic system. In this study, we develop a novel computational method for analyzing predicted flux distributions for metabolic reconstructions. Because chemical reactions may have multiple reactants and products, a directed hypergraph where...
Chapter
Liquid transportation fuels are used globally on a daily basis at a high consumption rate that is projected to rapidly increase over the next several decades. With dwindling, finite supplies of oil-based transportation fuels, there is an urgent need for alternative fuels. However, most proposed alternative fuels and fuel production schemes have pot...
Chapter
Biofuel production has the potential to have a great and lasting impact on the society and is a focal point of biological and metabolic engineering research. There have been great advances in the ability to engineer biological systems, and it can be seen that there lies many possibilities to expand the use of biology in producing a variety of chemi...
Chapter
Synthetic biology started with an emphasis in experimental molecular biology through the demonstration that characterized DNA sequences which can be taken out of their native context and re-implemented in novel ways. The scope of synthetic biology research has rapidly increased with the improvement and development of tools for direct DNA synthesis...
Article
Genome-scale metabolic models (GMMs) have been recognized as being powerful tools for capturing system-wide metabolic phenomena and connecting those phenomena to underlying genetic and regulatory changes. By formalizing and codifying the relationship between the levels of gene expression, protein concentration, and reaction flux, metabolic models a...
Chapter
Systems biology utilizes experimental and computational tools with a goal of understanding the intact, interconnected functionality of biological systems. The ability to comprehensively experimentally measure and computationally model all of the individual components in a cell has added new dimensions to our understanding of how cellular systems wo...
Chapter
Due to the diversity of impacts the fuel industry has on society, it is often difficult to comprehensively evaluate the benefits and drawbacks of any given fuel or fuel production process. This is especially true when the impacts influence disparate fields that have their own considerations and metrics that may not be compatible. The analysis frame...
Chapter
A critical step in engineering design is the ability to accurately construct something to directly translate a conceptual design to practice. Due to the relatively short history of molecular biology and the limitations in knowledge and technology, biological engineering has been hindered by a lack of ability to easily implement conceptual designs....
Chapter
Research approaches to developing biofuel processes involve the integration of different aspects of biology, chemistry, and engineering. Recent developments in knowledge and technology have enabled a shift away from discovery-based, trial-and-error design to a more directed prospective design process. Systems biology and synthetic biology have cont...
Article
Superficially, evolutionary engineering is a paradoxical field that balances competing interests. In natural settings, evolution iteratively selects and enriches subpopulations that are best adapted to a particular ecological niche using random processes such as genetic mutation. In engineering desired approaches utilize rational prospective design...
Article
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Constraint-based metabolic models are currently the most comprehensive system-wide models of cellular metabolism. Several challenges arise when building an in silico constraint-based model of an organism that need to be addressed before flux balance analysis (FBA) can be applied for simulations. An algorithm called FBA-Gap is presented here that ai...
Data
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The Supplementary Material contains a proof that FBA-Gap is NP-Complete and tables related to computational results. A list of low-cost exchange reactions is in Table S1. Results from the first round of FBA-Gap for B. subtilis, T. cruzi, H. pylori, E. coli, and C. neoformans are in Table S2. For the C. neoformans model, the _rst step of FBA-Gap yie...
Article
Stem-cell research seeks to address many different questions related to fundamental stem-cell function with the ultimate goal of being able to control and utilize stem cells for a broad range of therapeutic needs. While a large amount of work is focused on discovering and controlling differentiation mechanisms in stem cells, an equally interesting...
Article
A clear perception of gene essentiality in bacterial pathogens is pivotal for identifying drug targets to combat emergence of new pathogens and antibiotic-resistant bacteria, for synthetic biology, and for understanding the origins of life. We have constructed a comprehensive set of deletion mutants and systematically identified a clearly defined s...
Conference Paper
The production of chemicals in biological hosts has attracted significant academic and commercial interest in the past decades due to fossil fuels depletion and the necessity for a sustainable planet. Research has focused not only on low cost fuels, but also on value-added chemicals. Although there are many microorganisms naturally producing bioche...
Article
Full-text available
Biological utilization of cellulose is a complex process involving the coordinated expression of different cellulases, often in a synergistic manner. One possible means of inducing an organism-level change in cellulase activity is to use laboratory adaptive evolution. In this study, evolved strains of the cellulolytic actinobacterium, Thermobifida...
Article
Harnessing the immense natural diversity of biological functions for economical production of fuel has enormous potential benefits. Inevitably, however, the native capabilities for any given organism must be modified to increase the productivity or efficiency of a biofuel bioprocess. From a broad perspective, the challenge is to sufficiently unders...
Article
Biofuel production from renewable resources can potentially address lots of social, economic and environmental issues but an efficient production method has yet to be established. Combinations of different starting materials, organisms and target fuels have been explored with the conversion of cellulose to higher alcohols (1-propanol, 1-butanol) be...
Article
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Synthetic Biology is the new engineering-based approach to biology that includes applications of designing complex biological devices. At present, it is not yet clear what will emerge as the defining principles of Synthetic Biology. One proposed approach is to build Synthetic Biology around the classical engineering principles of standardization, m...
Conference Paper
One of the most important issues facing this generation is that of sustainability. Research to identify sustainable alternatives for fossil fuels has been extensive, with ethanol receiving most of the attention. However, a less corrosive, less volatile substitute has been found in butanol, a four carbon alcohol which contains more energy per kilogr...
Article
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The field of synthetic biology has made rapid progress in a number of areas including method development, novel applications and community building. In seeking to make biology "engineerable," synthetic biology is increasing the accessibility of biological research to researchers of all experience levels and backgrounds. One of the underlying streng...
Article
Constraint-based genome-scale metabolic models are becoming an established tool for using genomic and biochemical information to predict cellular phenotypes. While these models provide quantitative predictions for individual reactions and are readily scalable for any biological system, they have inherent limitations. Using current methods, it is di...
Article
The apicomplexan Cryptosporidium is a protozoan parasite of humans and other mammals. Cryptosporidium species cause acute gastroenteritis and diarrheal disease in healthy humans and animals, and cause life-threatening infection in immunocompromised individuals such as people with AIDS. The parasite has a one-host life cycle and commonly invades int...
Article
Industrial production of solvents such as EtOH and BuOH from cellulosic biomass has the potential to provide a sustainable energy source that is relatively cheap, abundant, and environmentally sound, but currently production costs are driven up by expensive enzymes, which are necessary to degrade cellulose into fermentable sugars. These costs could...
Article
Two strategies for fighting cancer by modulating FASL-induced apoptosis were modeled by 2D-cellular automata. Our models predict that cancer cells can be killed by maximizing the apoptosis via joint suppression of FLIP and IAP inhibitors by siRNA and SMAC proteins, respectively. It was also predicted that the presumed feedback loop CASP3-->CASP9-->...