@article{Gushgari-Doyle2022,

title = {Genotype to ecotype in niche environments: adaptation of Arthrobacter to carbon availability and environmental conditions},

author = {Sara Gushgari-Doyle and Lauren M. Lui and Torben N. Nielsen and Xiaoqin Wu and Ria G. Malana and Andrew J. Hendrickson and Heloise Carion and Farris L. Poole and Michael W. W. Adams and Adam P. Arkin and Romy Chakraborty},

doi = {10.1038/s43705-022-00113-8},

issn = {2730-6151},

year  = {2022},

date = {2022-12-00},

journal = {ISME COMMUN.},

volume = {2},

number = {1},

publisher = {Oxford University Press (OUP)},

abstract = {AbstractNiche environmental conditions influence both the structure and function of microbial communities and the cellular function of individual strains. The terrestrial subsurface is a dynamic and diverse environment that exhibits specific biogeochemical conditions associated with depth, resulting in distinct environmental niches. Here, we present the characterization of seven distinct strains belonging to the genus Arthrobacter isolated from varying depths of a single sediment core and associated groundwater from an adjacent well. We characterized genotype and phenotype of each isolate to connect specific cellular functions and metabolisms to ecotype. Arthrobacter isolates from each ecotype demonstrated functional and genomic capacities specific to their biogeochemical conditions of origin, including laboratory-demonstrated characterization of salinity tolerance and optimal pH, and genes for utilization of carbohydrates and other carbon substrates. Analysis of the Arthrobacter pangenome revealed that it is notably open with a volatile accessory genome compared to previous pangenome studies on other genera, suggesting a high potential for adaptability to environmental niches.},

keywords = {Automotive Engineering},

pubstate = {published},

tppubtype = {article}

}

@article{Chivian2022b,

title = {Publisher Correction: Metagenome-assembled genome extraction and analysis from microbiomes using KBase},

author = {Dylan Chivian and Sean P. Jungbluth and Paramvir S. Dehal and Elisha M. Wood-Charlson and Richard S. Canon and Benjamin H. Allen and Mikayla M. Clark and Tianhao Gu and Miriam L. Land and Gavin A. Price and William J. Riehl and Michael W. Sneddon and Roman Sutormin and Qizhi Zhang and Robert W. Cottingham and Chris S. Henry and Adam P. Arkin},

doi = {10.1038/s41596-022-00794-4},

issn = {1750-2799},

year  = {2022},

date = {2022-11-30},

journal = {Nat Protoc},

publisher = {Springer Science and Business Media LLC},

keywords = {General Biochemistry, Genetics and Molecular Biology},

pubstate = {published},

tppubtype = {article}

}

@article{Goff2022b,

title = {Ecophysiological and genomic analyses of a representative isolate of highly abundant \textit{Bacillus cereus} strains in contaminated subsurface sediments},

author = {Jennifer L. Goff and Elizabeth G. Szink and Michael P. Thorgersen and Andrew D. Putt and Yupeng Fan and Lauren M. Lui and Torben N. Nielsen and Kristopher A. Hunt and Jonathan P. Michael and Yajiao Wang and Daliang Ning and Ying Fu and Joy D. Van Nostrand and Farris L. Poole and John‐Marc Chandonia and Terry C. Hazen and David A. Stahl and Jizhong Zhou and Adam P. Arkin and Michael W. W. Adams},

doi = {10.1111/1462-2920.16173},

issn = {1462-2920},

year  = {2022},

date = {2022-11-00},

journal = {Environmental Microbiology},

volume = {24},

number = {11},

pages = {5546--5560},

publisher = {Wiley},

abstract = {AbstractBacillus cereus strain CPT56D‐587‐MTF (CPTF) was isolated from the highly contaminated Oak Ridge Reservation (ORR) subsurface. This site is contaminated with high levels of nitric acid and multiple heavy metals. Amplicon sequencing of the 16S rRNA genes (V4 region) in sediment from this area revealed an amplicon sequence variant (ASV) with 100% identity to the CPTF 16S rRNA sequence. Notably, this CPTF‐matching ASV had the highest relative abundance in this community survey, with a median relative abundance of 3.77% and comprised 20%–40% of reads in some samples. Pangenomic analysis revealed that strain CPTF has expanded genomic content compared to other B. cereus species—largely due to plasmid acquisition and expansion of transposable elements. This suggests that these features are important for rapid adaptation to native environmental stressors. We connected genotype to phenotype in the context of the unique geochemistry of the site. These analyses revealed that certain genes (e.g. nitrate reductase, heavy metal efflux pumps) that allow this strain to successfully occupy the geochemically heterogenous microniches of its native site are characteristic of the B. cereus species while others such as acid tolerance are mobile genetic element associated and are generally unique to strain CPTF.},

keywords = {Behavior and Systematics, Ecology, Evolution, Microbiology},

pubstate = {published},

tppubtype = {article}

}

@article{Wood-Charlson2022,

title = {Ten simple rules for getting and giving credit for data},

author = {Elisha M. Wood-Charlson and Zachary Crockett and Chris Erdmann and Adam P. Arkin and Carly B. Robinson},

editor = {Russell Schwartz},

doi = {10.1371/journal.pcbi.1010476},

issn = {1553-7358},

year  = {2022},

date = {2022-09-29},

journal = {PLoS Comput Biol},

volume = {18},

number = {9},

publisher = {Public Library of Science (PLoS)},

keywords = {Behavior and Systematics, Cellular and Molecular Neuroscience, Computational Theory and Mathematics, Ecology, Evolution, Genetics, Modeling and Simulation, Molecular Biology},

pubstate = {published},

tppubtype = {article}

}

@article{Tao2022,

title = {Development of a Markerless Deletion Mutagenesis System in Nitrate-Reducing Bacterium Rhodanobacter denitrificans},

author = {Xuanyu Tao and Aifen Zhou and Megan L. Kempher and Jiantao Liu and Mu Peng and Yuan Li and Jonathan P. Michael and Romy Chakraborty and Adam M. Deutschbauer and Adam P. Arkin and Jizhong Zhou},

editor = {Arpita Bose},

doi = {10.1128/aem.00401-22},

issn = {1098-5336},

year  = {2022},

date = {2022-07-26},

journal = {Appl Environ Microbiol},

volume = {88},

number = {14},

publisher = {American Society for Microbiology},

abstract = {

            Rhodanobacter denitrificans

            is capable of denitrification and is also resistant to toxic heavy metals and low pH. Accordingly, the presence of

            Rhodanobacter

            species at a particular environmental site is considered an indicator of nitrate and uranium contamination.

          },

keywords = {Applied Microbiology and Biotechnology, Biotechnology, Ecology, Food Science},

pubstate = {published},

tppubtype = {article}

}

@article{Abel2022,

title = {Systems-informed genome mining for electroautotrophic microbial production},

author = {Anthony J. Abel and Jacob M. Hilzinger and Adam P. Arkin and Douglas S. Clark},

doi = {10.1016/j.bioelechem.2022.108054},

issn = {1567-5394},

year  = {2022},

date = {2022-06-00},

journal = {Bioelectrochemistry},

volume = {145},

publisher = {Elsevier BV},

keywords = {Biophysics, Electrochemistry, General Medicine, Physical and Theoretical Chemistry},

pubstate = {published},

tppubtype = {article}

}

@article{deRaad2022,

title = {A Defined Medium for Cultivation and Exometabolite Profiling of Soil Bacteria},

author = {Markus de Raad and Yifan V. Li and Jennifer V. Kuehl and Peter F. Andeer and Suzanne M. Kosina and Andrew Hendrickson and Nicholas R. Saichek and Amber N. Golini and La Zhen Han and Ying Wang and Benjamin P. Bowen and Adam M. Deutschbauer and Adam P. Arkin and Romy Chakraborty and Trent R. Northen},

doi = {10.3389/fmicb.2022.855331},

issn = {1664-302X},

year  = {2022},

date = {2022-05-25},

journal = {Front. Microbiol.},

volume = {13},

publisher = {Frontiers Media SA},

abstract = {Exometabolomics is an approach to assess how microorganisms alter, or react to their environments through the depletion and production of metabolites. It allows the examination of how soil microbes transform the small molecule metabolites within their environment, which can be used to study resource competition and cross-feeding. This approach is most powerful when used with defined media that enable tracking of all metabolites. However, microbial growth media have traditionally been developed for the isolation and growth of microorganisms but not metabolite utilization profiling through Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Here, we describe the construction of a defined medium, the Northen Lab Defined Medium (NLDM), that not only supports the growth of diverse soil bacteria but also is defined and therefore suited for exometabolomic experiments. Metabolites included in NLDM were selected based on their presence in R2A medium and soil, elemental stoichiometry requirements, as well as knowledge of metabolite usage by different bacteria. We found that NLDM supported the growth of 108 of the 110 phylogenetically diverse (spanning 36 different families) soil bacterial isolates tested and all of its metabolites were trackable through LC–MS/MS analysis. These results demonstrate the viability and utility of the constructed NLDM medium for growing and characterizing diverse microbial isolates and communities.},

keywords = {Microbiology, Microbiology (medical)},

pubstate = {published},

tppubtype = {article}

}

@article{Goff2022,

title = {Complete Genome Sequence of Bacillus cereus Strain CPT56D-587-MTF, Isolated from a Nitrate- and Metal-Contaminated Subsurface Environment},

author = {Jennifer L. Goff and Lauren M. Lui and Torben N. Nielsen and Michael P. Thorgersen and Elizabeth G. Szink and John-Marc Chandonia and Farris L. Poole and Jizhong Zhou and Terry C. Hazen and Adam P. Arkin and Michael W. W. Adams},

editor = {Steven R. Gill},

doi = {10.1128/mra.00145-22},

issn = {2576-098X},

year  = {2022},

date = {2022-05-19},

journal = {Microbiol Resour Announc},

volume = {11},

number = {5},

publisher = {American Society for Microbiology},

abstract = {

            Bacillus cereus

            strain CPT56D-587-MTF was isolated from nitrate- and toxic metal-contaminated subsurface sediment at the Oak Ridge Reservation (ORR) (Oak Ridge, TN, USA). Here, we report the complete genome sequence of this strain to provide genomic insight into its strategies for survival at this mixed-waste site.

          },

keywords = {Genetics, Immunology and Microbiology (miscellaneous), Molecular Biology},

pubstate = {published},

tppubtype = {article}

}

@article{Price2022b,

title = {Filling gaps in bacterial catabolic pathways with computation and high-throughput genetics},

author = {Morgan N. Price and Adam M. Deutschbauer and Adam P. Arkin},

editor = {Bernhard O. Palsson},

doi = {10.1371/journal.pgen.1010156},

issn = {1553-7404},

year  = {2022},

date = {2022-04-13},

journal = {PLoS Genet},

volume = {18},

number = {4},

publisher = {Public Library of Science (PLoS)},

abstract = {To discover novel catabolic enzymes and transporters, we combined high-throughput genetic data from 29 bacteria with an automated tool to find gaps in their catabolic pathways. GapMind for carbon sources automatically annotates the uptake and catabolism of 62 compounds in bacterial and archaeal genomes. For the compounds that are utilized by the 29 bacteria, we systematically examined the gaps in GapMind’s predicted pathways, and we used the mutant fitness data to find additional genes that were involved in their utilization. We identified novel pathways or enzymes for the utilization of glucosamine, citrulline, myo-inositol, lactose, and phenylacetate, and we annotated 299 diverged enzymes and transporters. We also curated 125 proteins from published reports. For the 29 bacteria with genetic data, GapMind finds high-confidence paths for 85% of utilized carbon sources. In diverse bacteria and archaea, 38% of utilized carbon sources have high-confidence paths, which was improved from 27% by incorporating the fitness-based annotations and our curation. GapMind for carbon sources is available as a web server (http://papers.genomics.lbl.gov/carbon) and takes just 30 seconds for the typical genome.},

keywords = {Behavior and Systematics, Cancer Research, Ecology, Evolution, Genetics, Genetics (clinical), Molecular Biology},

pubstate = {published},

tppubtype = {article}

}

@article{Mutalik2022,

title = {A Phage Foundry Framework to Systematically Develop Viral Countermeasures to Combat Antibiotic-Resistant Bacterial Pathogens},

author = {Vivek K. Mutalik and Adam P. Arkin},

doi = {10.1016/j.isci.2022.104121},

issn = {2589-0042},

year  = {2022},

date = {2022-04-00},

journal = {iScience},

volume = {25},

number = {4},

publisher = {Elsevier BV},

keywords = {Multidisciplinary},

pubstate = {published},

tppubtype = {article}

}

@article{Peng2022,

title = {Genomic Features and Pervasive Negative Selection in

            \textit{Rhodanobacter}

            Strains Isolated from Nitrate and Heavy Metal Contaminated Aquifer},

author = {Mu Peng and Dongyu Wang and Lauren M. Lui and Torben Nielsen and Renmao Tian and Megan L. Kempher and Xuanyu Tao and Chongle Pan and Romy Chakraborty and Adam M. Deutschbauer and Michael P. Thorgersen and Michael W. W. Adams and Matthew W. Fields and Terry C. Hazen and Adam P. Arkin and Aifen Zhou and Jizhong Zhou},

editor = {Kristen M. DeAngelis},

doi = {10.1128/spectrum.02591-21},

issn = {2165-0497},

year  = {2022},

date = {2022-02-23},

journal = {Microbiol Spectr},

volume = {10},

number = {1},

publisher = {American Society for Microbiology},

abstract = {

            Despite the dominance of

            Rhodanobacter

            species in the subsurface of the contaminated Oak Ridge Reservation (ORR) site, very little is known about the mechanisms underlying their adaptions to the various stressors present at ORR. Recently, multiple

            Rhodanobacter

            strains have been isolated from the ORR groundwater samples from several wells with varying geochemical properties.

          },

keywords = {Cell Biology, Ecology, General Immunology and Microbiology, Genetics, Infectious Diseases, Microbiology (medical), Physiology},

pubstate = {published},

tppubtype = {article}

}

@article{McCausland2022,

title = {Global Analysis of Biomineralization Genes in

            \textit{Magnetospirillum magneticum}

            AMB-1},

author = {Hayley C. McCausland and Kelly M. Wetmore and Adam P. Arkin and Arash Komeili},

editor = {Sarah Glaven},

doi = {10.1128/msystems.01037-21},

issn = {2379-5077},

year  = {2022},

date = {2022-02-22},

journal = {mSystems},

volume = {7},

number = {1},

publisher = {American Society for Microbiology},

abstract = {Magnetotactic bacteria (MTB) are a group of bacteria that can form nano-sized crystals of magnetic minerals. MTB are likely an important part of their ecosystems, because they can account for up to a third of the microbial biomass in an aquatic habitat and consume large amounts of iron, potentially impacting the iron cycle.},

keywords = {Behavior and Systematics, Biochemistry, Computer Science Applications, Ecology, Evolution, Genetics, Microbiology, Modeling and Simulation, Molecular Biology, Physiology},

pubstate = {published},

tppubtype = {article}

}

@article{Paradis2021,

title = {Sustained Ability of a Natural Microbial Community to Remove Nitrate from Groundwater},

author = {Charles J. Paradis and John I. Miller and Ji‐Won Moon and Sarah J. Spencer and Lauren M. Lui and Joy D. Van Nostrand and Daliang Ning and Andrew D. Steen and Larry D. McKay and Adam P. Arkin and Jizhong Zhou and Eric J. Alm and Terry C. Hazen},

doi = {10.1111/gwat.13132},

issn = {1745-6584},

year  = {2022},

date = {2022-01-00},

journal = {Groundwater},

volume = {60},

number = {1},

pages = {99--111},

publisher = {Wiley},

abstract = {AbstractMicrobial‐mediated nitrate removal from groundwater is widely recognized as the predominant mechanism for nitrate attenuation in contaminated aquifers and is largely dependent on the presence of a carbon‐bearing electron donor. The repeated exposure of a natural microbial community to an electron donor can result in the sustained ability of the community to remove nitrate; this phenomenon has been clearly demonstrated at the laboratory scale. However, in situ demonstrations of this ability are lacking. For this study, ethanol (electron donor) was repeatedly injected into a groundwater well (treatment) for six consecutive weeks to establish the sustained ability of a microbial community to remove nitrate. A second well (control) located upgradient was not injected with ethanol during this time. The treatment well demonstrated strong evidence of sustained ability as evident by ethanol, nitrate, and subsequent sulfate removal up to 21, 64, and 68%, respectively, as compared to the conservative tracer (bromide) upon consecutive exposures. Both wells were then monitored for six additional weeks under natural (no injection) conditions. During the final week, ethanol was injected into both treatment and control wells. The treatment well demonstrated sustained ability as evident by ethanol and nitrate removal up to 20 and 21%, respectively, as compared to bromide, whereas the control did not show strong evidence of nitrate removal (5% removal). Surprisingly, the treatment well did not indicate a sustained and selective enrichment of a microbial community. These results suggested that the predominant mechanism(s) of sustained ability likely exist at the enzymatic‐ and/or genetic‐levels. The results of this study demonstrated the in situ ability of a microbial community to remove nitrate can be sustained in the prolonged absence of an electron donor.},

keywords = {Computers in Earth Sciences, Water Science and Technology},

pubstate = {published},

tppubtype = {article}

}

@article{Novichkov2022,

title = {CORAL: A framework for rigorous self-validated data modeling and integrative, reproducible data analysis},

author = {Pavel S Novichkov and John-Marc Chandonia and Adam P Arkin},

doi = {10.1093/gigascience/giac089},

issn = {2047-217X},

year  = {2022},

date = {2022-00-00},

volume = {11},

publisher = {Oxford University Press (OUP)},

abstract = {Abstract

               

                  Background

                  Many organizations face challenges in managing and analyzing data, especially when relevant datasets arise from multiple sources and methods. Analyzing heterogeneous datasets and additional derived data requires rigorous tracking of their interrelationships and provenance. This task has long been a Grand Challenge of data science and has more recently been formalized in the FAIR principles: that all data objects be Findable, Accessible, Interoperable, and Reusable, both for machines and for people. Adherence to these principles is necessary for proper stewardship of information, for testing regulatory compliance, for measuring the efficiency of processes, and for facilitating reuse of data-analytical frameworks.

               

               

                  Findings

                  We present the Contextual Ontology-based Repository Analysis Library (CORAL), a platform that greatly facilitates adherence to all 4 of the FAIR principles, including the especially difficult challenge of making heterogeneous datasets Interoperable and Reusable across all parts of a large, long-lasting organization. To achieve this, CORAL's data model requires that data generators extensively document the context for all data, and our tools maintain that context throughout the entire analysis pipeline. CORAL also features a web interface for data generators to upload and explore data, as well as a Jupyter notebook interface for data analysts, both backed by a common API.

               

               

                  Conclusions

                  CORAL enables organizations to build FAIR data types on the fly as they are needed, avoiding the expense of bespoke data modeling. CORAL provides a uniquely powerful platform to enable integrative cross-dataset analyses, generating deeper insights than are possible using traditional analysis tools.

               },

keywords = {Computer Science Applications, Health Informatics},

pubstate = {published},

tppubtype = {article}

}

@article{Kosina2021,

title = {Biofilm Interaction Mapping and Analysis (BIMA) of Interspecific Interactions in Pseudomonas Co-culture Biofilms},

author = {Suzanne M. Kosina and Peter Rademacher and Kelly M. Wetmore and Markus de Raad and Marcin Zemla and Grant M. Zane and Jennifer J. Zulovich and Romy Chakraborty and Benjamin P. Bowen and Judy D. Wall and Manfred Auer and Adam P. Arkin and Adam M. Deutschbauer and Trent R. Northen},

doi = {10.3389/fmicb.2021.757856},

issn = {1664-302X},

year  = {2021},

date = {2021-12-09},

journal = {Front. Microbiol.},

volume = {12},

publisher = {Frontiers Media SA},

abstract = {Pseudomonas species are ubiquitous in nature and include numerous medically, agriculturally and technologically beneficial strains of which the interspecific interactions are of great interest for biotechnologies. Specifically, co-cultures containing Pseudomonas stutzeri have been used for bioremediation, biocontrol, aquaculture management and wastewater denitrification. Furthermore, the use of P. stutzeri biofilms, in combination with consortia-based approaches, may offer advantages for these processes. Understanding the interspecific interaction within biofilm co-cultures or consortia provides a means for improvement of current technologies. However, the investigation of biofilm-based consortia has been limited. We present an adaptable and scalable method for the analysis of macroscopic interactions (colony morphology, inhibition, and invasion) between colony-forming bacterial strains using an automated printing method followed by analysis of the genes and metabolites involved in the interactions. Using Biofilm Interaction Mapping and Analysis (BIMA), these interactions were investigated between P. stutzeri strain RCH2, a denitrifier isolated from chromium (VI) contaminated soil, and 13 other species of pseudomonas isolated from non-contaminated soil. One interaction partner, Pseudomonas fluorescens N1B4 was selected for mutant fitness profiling of a DNA-barcoded mutant library; with this approach four genes of importance were identified and the effects on interactions were evaluated with deletion mutants and mass spectrometry based metabolomics.},

keywords = {Microbiology, Microbiology (medical)},

pubstate = {published},

tppubtype = {article}

}

@article{Adler2021,

title = {The genetic basis of phage susceptibility, cross-resistance and host-range in Salmonella},

author = {Benjamin A. Adler and Alexey E. Kazakov and Crystal Zhong and Hualan Liu and Elizabeth Kutter and Lauren M. Lui and Torben N. Nielsen and Heloise Carion and Adam M. Deutschbauer and Vivek K. Mutalik and Adam P. Arkin},

doi = {10.1099/mic.0.001126},

issn = {1465-2080},

year  = {2021},

date = {2021-12-01},

volume = {167},

number = {12},

publisher = {Microbiology Society},

abstract = {Though bacteriophages (phages) are known to play a crucial role in bacterial fitness and virulence, our knowledge about the genetic basis of their interaction, cross-resistance and host-range is sparse. Here, we employed genome-wide screens in 

                     

                        Salmonella enterica

                     

                   serovar Typhimurium to discover host determinants involved in resistance to eleven diverse lytic phages including four new phages isolated from a therapeutic phage cocktail. We uncovered 301 diverse host factors essential in phage infection, many of which are shared between multiple phages demonstrating potential cross-resistance mechanisms. We validate many of these novel findings and uncover the intricate interplay between RpoS, the virulence-associated general stress response sigma factor and RpoN, the nitrogen starvation sigma factor in phage cross-resistance. Finally, the infectivity pattern of eleven phages across a panel of 23 genome sequenced 

                     

                        Salmonella

                     

                   strains indicates that additional constraints and interactions beyond the host factors uncovered here define the phage host range.},

keywords = {Microbiology},

pubstate = {published},

tppubtype = {article}

}

@article{Thorgersen2021,

title = {Deciphering Microbial Metal Toxicity Responses via Random Bar Code Transposon Site Sequencing and Activity-Based Metabolomics},

author = {Michael P. Thorgersen and Jingchuan Xue and Erica L. W. Majumder and Valentine V. Trotter and Xiaoxuan Ge and Farris L. Poole and Trenton K. Owens and Lauren M. Lui and Torben N. Nielsen and Adam P. Arkin and Adam M. Deutschbauer and Gary Siuzdak and Michael W. W. Adams},

editor = {Rebecca E. Parales},

doi = {10.1128/aem.01037-21},

issn = {1098-5336},

year  = {2021},

date = {2021-10-14},

journal = {Appl Environ Microbiol},

volume = {87},

number = {21},

publisher = {American Society for Microbiology},

abstract = {

            Studying microbial interactions with their environment can lead to a deeper understanding of biological molecular mechanisms. In the manuscript, two global techniques, RB-TnSeq and activity metabolomics, were successfully used to probe the interactions between a metal-resistant microorganism,

            Pantoea

            sp. strain MT58, and metals contaminating a site where the organism can be located.

          },

keywords = {Applied Microbiology and Biotechnology, Biotechnology, Ecology, Food Science},

pubstate = {published},

tppubtype = {article}

}

@article{McNulty2021b,

title = {Evaluating the Cost of Pharmaceutical Purification for a Long-Duration Space Exploration Medical Foundry},

author = {Matthew J. McNulty and Aaron J. Berliner and Patrick G. Negulescu and Liber McKee and Olivia Hart and Kevin Yates and Adam P. Arkin and Somen Nandi and Karen A. McDonald},

doi = {10.3389/fmicb.2021.700863},

issn = {1664-302X},

year  = {2021},

date = {2021-10-11},

journal = {Front. Microbiol.},

volume = {12},

publisher = {Frontiers Media SA},

abstract = {There are medical treatment vulnerabilities in longer-duration space missions present in the current International Space Station crew health care system with risks, arising from spaceflight-accelerated pharmaceutical degradation and resupply lag times. Bioregenerative life support systems may be a way to close this risk gap by leveraging in situ resource utilization (ISRU) to perform pharmaceutical synthesis and purification. Recent literature has begun to consider biological ISRU using microbes and plants as the basis for pharmaceutical life support technologies. However, there has not yet been a rigorous analysis of the processing and quality systems required to implement biologically produced pharmaceuticals for human medical treatment. In this work, we use the equivalent system mass (ESM) metric to evaluate pharmaceutical purification processing strategies for longer-duration space exploration missions. Monoclonal antibodies, representing a diverse therapeutic platform capable of treating multiple space-relevant disease states, were selected as the target products for this analysis. We investigate the ESM resource costs (mass, volume, power, cooling, and crew time) of an affinity-based capture step for monoclonal antibody purification as a test case within a manned Mars mission architecture. We compare six technologies (three biotic capture methods and three abiotic capture methods), optimize scheduling to minimize ESM for each technology, and perform scenario analysis to consider a range of input stream compositions and pharmaceutical demand. We also compare the base case ESM to scenarios of alternative mission configuration, equipment models, and technology reusability. Throughout the analyses, we identify key areas for development of pharmaceutical life support technology and improvement of the ESM framework for assessment of bioregenerative life support technologies.},

keywords = {Microbiology, Microbiology (medical)},

pubstate = {published},

tppubtype = {article}

}

@article{McNulty2021,

title = {Molecular pharming to support human life on the moon, mars, and beyond},

author = {Matthew J. McNulty and Yongao (Mary) Xiong and Kevin Yates and Kalimuthu Karuppanan and Jacob M. Hilzinger and Aaron J. Berliner and Jesse Delzio and Adam P. Arkin and Nancy E. Lane and Somen Nandi and Karen A. McDonald},

doi = {10.1080/07388551.2021.1888070},

issn = {1549-7801},

year  = {2021},

date = {2021-08-18},

journal = {Critical Reviews in Biotechnology},

volume = {41},

number = {6},

pages = {849--864},

publisher = {Informa UK Limited},

keywords = {Applied Microbiology and Biotechnology, Biotechnology, General Medicine},

pubstate = {published},

tppubtype = {article}

}

@article{Skerker2021,

title = {Chromosome assembled and annotated genome sequence of \textit{Aspergillus flavus} NRRL 3357},

author = {Jeffrey M Skerker and Kaila M Pianalto and Stephen J Mondo and Kunlong Yang and Adam P Arkin and Nancy P Keller and Igor V Grigoriev and N Louise Glass},

editor = {J C Dunlap},

doi = {10.1093/g3journal/jkab213},

issn = {2160-1836},

year  = {2021},

date = {2021-08-07},

volume = {11},

number = {8},

publisher = {Oxford University Press (OUP)},

abstract = {Abstract

               Aspergillus flavus is an opportunistic pathogen of crops, including peanuts and maize, and is the second leading cause of aspergillosis in immunocompromised patients. A. flavus is also a major producer of the mycotoxin, aflatoxin, a potent carcinogen, which results in significant crop losses annually. The A. flavus isolate NRRL 3357 was originally isolated from peanut and has been used as a model organism for understanding the regulation and production of secondary metabolites, such as aflatoxin. A draft genome of NRRL 3357 was previously constructed, enabling the development of molecular tools and for understanding population biology of this particular species. Here, we describe an updated, near complete, telomere-to-telomere assembly and re-annotation of the eight chromosomes of A. flavus NRRL 3357 genome, accomplished via long-read PacBio and Oxford Nanopore technologies combined with Illumina short-read sequencing. A total of 13,715 protein-coding genes were predicted. Using RNA-seq data, a significant improvement was achieved in predicted 5’ and 3’ untranslated regions, which were incorporated into the new gene models.},

keywords = {Genetics, Genetics (clinical), Molecular Biology},

pubstate = {published},

tppubtype = {article}

}