
James W. Golden
· ProfessorVerifiedUniversity of California, San Diego · Molecular Biology
Active 1949–2026
About
Dr. James W. Golden received a B.S. in Microbiology from the University of Maryland-College Park in 1977 and a Ph.D. in Biology from the University of Missouri-Columbia in 1983. After completing postdoctoral work as an NIH Fellow at The University of Chicago, he joined the Department of Biology at Texas A&M University in 1986, where he was promoted to Associate Professor in 1990 and then to Professor in 1996. In 2008, Dr. Golden moved to the University of California, San Diego. His research focuses on the genetics, molecular biology, and biotechnology of cyanobacteria, including developing improved genetic tools for cyanobacterial genetic engineering and applying these tools to basic science questions and biotechnology applications. His work involves genetic engineering of cyanobacteria to synthesize bioactive natural products and biofuels, as well as studying genes related to resistance to predators, toxin biosynthesis, and growth fitness during spaceflight or on Mars. His research has included developmental biology of cyanobacterial heterocyst formation, regulation of cellular differentiation, and cell-to-cell signaling mechanisms in multicellular cyanobacteria such as Anabaena. Dr. Golden's work employs genetics and molecular biology methods to understand regulation and signaling pathways in simple prokaryotic multicellular organisms.
Research topics
- Biology
- Genetics
- Computational biology
- Neuroscience
- Cell biology
- Botany
Selected publications
Polymerization of 3D Printable PEDOT:PSS Catalyzed by Cyanobacteria
ACS Sustainable Chemistry & Engineering · 2026-03-25
articleSustainable chemical synthesis is important to reduce hazardous reagents and minimize their environmental impact. Most biocatalytic approaches rely on purified enzymes or engineered microbes. In contrast, this study uses wild-type photosynthetic cyanobacteria to directly drive polymerization, harnessing naturally produced redox mediators for conductive-material synthesis. The biocatalytic polymerization of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) by the cyanobacterium Synechococcus elongatus (PCC 7942) and its secreted byproducts is described herein. Polymer yield was modulated by growing cells in either continuous light or varied light/dark cycles, suggesting a link between the accumulation of redox mediators and reaction kinetics. Both whole-cell cultures and conditioned media derived from these cultures produced PEDOT:PSS. Treatment of the conditioned media with proteinase K and autoclaving still resulted in polymerization, indicating that the reaction is not enzyme-dependent. Viscosity measurements showed shear-thinning behavior of the resulting conductive ink, consistent with extrusion and printability by using direct ink writing printing. The material was optimized for printing into self-supporting 3D structures and exhibited an average conductivity of 1.19 × 10–5 S/cm. These findings demonstrate the potential of photosynthetic microbial byproducts as sustainable alternatives for polymer synthesis.
bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-30
articleOpen accessSenior authorCorrespondingAbstract Cyanobacteria have garnered interest as promising biological platforms for producing renewable biofuel, chemical feedstock, and bioactive molecules. For biotechnology applications, robust well-characterized genetic tools are required for genetically modifying cyanobacteria, but these tools are often developed for specific model strains. Here, we used broad host-range RSF1010-based plasmids to characterize a set of orthogonal constitutive promoters in diverse cyanobacterial strains. The promoters are random variants of the synthetic Escherichia coli PconII promoter. A library of PconII promoters driving a fluorescent reporter gene was first evaluated in Synechococcus elongatus and found to have a wide range of gene expression levels. A set of 25 promoter variants with graded strengths was selected after characterization in S. elongatus and three additional model cyanobacterial strains. To demonstrate the utility of these promoters, we isolated new genetically tractable cyanobacterial strains with high salt and alkalinity tolerance and transferred the subset of promoters into one of these newly isolated strains. Similar to the results with model strains, the subset of promoters had a wide range of expression levels in the non-model strain. These characterized promoters expand the genetic tools available for genetic engineering of model and non-model cyanobacterial strains. Importance The use of cyanobacteria to produce renewable products will require engineered expression of many genes that affect cell growth, metabolism, and agronomic properties, leading to efficient production of biomass and desired products. Engineering the strength of gene transcription is an important element of overall gene expression levels. The set of constitutive promoters described here, with a wide range of expression strengths characterized in several diverse cyanobacterial strains, provides an important resource for genetic engineering required for biotechnology applications. Research Areas Microbial genetics, plasmids and other genetic constructs, biotechnology Journal Secction Biotechnology
Proceedings of the National Academy of Sciences · 2025-05-01 · 1 citations
articleOpen accessStimuli-responsive engineered living materials (ELMs) can respond to environmental or biochemical cues and have broad utility in biological sensors and machines, but have traditionally been limited to biocompatible scaffolds. This is because they are typically made by mixing cells into a precursor solution before crosslinking. Here, we demonstrate a diffusion mechanism for incorporating cells of the cyanobacterium Synechococcus elongatus sp. PCC 7942 ( S. elongatus ) into nanoclay-poly-N-isopropylacrylamide (NC-PNIPAm), a hydrogel with a cytotoxic precursor, by exploiting its temperature-dependent shape-morphing behavior. Subsequent growth of S. elongatus caused a decrease in the bending curvature and stiffness (local Young’s modulus) of NC-PNIPAm due to partial degradation by an unannotated enzyme. Creation and observation of this cyanobacteria-hydrogel ELM showcases a method for diffusing cells into a hydrogel as well as characterizing an extracellular enzyme.
mBio · 2023-10-04 · 8 citations
articleOpen accessABSTRACT The cyanobacterium Synechococcus elongatus PCC 7942 produces an active prokaryotic Argonaute nuclease, SeAgo, whose function is unknown. Here, we show that SeAgo reduces natural transformation and prevents the maintenance of RSF1010 replicons in S. elongatus . In addition, a Cas4-like nuclease and two other proteins, UvrD and RecJ cy (cyanobacterial lineage), were found to reduce the transfer or maintenance of RSF1010 replicons. Like other prokaryotic Argonautes, our results indicate that SeAgo provides defense against invading DNA. An S. elongatus ago deletion strain shares the same morphology, growth rate, and circadian gene expression as the wild type, has higher transformation efficiency, and enables the use of RSF1010-based plasmids for genetic engineering. IMPORTANCE S. elongatus is an important cyanobacterial model organism for the study of its prokaryotic circadian clock, photosynthesis, and other biological processes. It is also widely used for genetic engineering to produce renewable biochemicals. Our findings reveal an SeAgo-based defense mechanism in S. elongatus against the horizontal transfer of genetic material. We demonstrate that deletion of the ago gene facilitates genetic studies and genetic engineering of S. elongatus .
Phenotypically Complex Living Materials Containing Engineered Cyanobacteria
bioRxiv (Cold Spring Harbor Laboratory) · 2023-01-27 · 3 citations
preprintOpen accessSummary A cyanobacterial photosynthetic biocomposite material was fabricated using 3D-printing and bioengineered to produce multiple functional outputs in response to an external chemical stimulus. Our investigations show the advantages of utilizing additive manufacturing techniques in controlling the design and shape of the fabricated materials, which proved to be important for the support and growth of obligate phototrophic microorganisms within the material. As an initial proof-of-concept, a synthetic theophylline-responsive riboswitch in Synechococcus elongatus PCC 7942 was used for regulating the expression of a yellow fluorescent protein (YFP) reporter. Upon induction with theophylline, the encapsulated cells produced YFP within the hydrogel matrix. Subsequently, a strain of S. elongatus was engineered to produce an oxidative enzyme that is useful for bioremediation, laccase, expressed either constitutively or under the control of the riboswitch. The responsive biomaterial can decolorize a common textile dye pollutant, indigo carmine, potentially serving as a useful tool in environmental bioremediation. Finally, cells were engineered to have the capacity for inducible cell death to eliminate their presence once their activity is no longer required, which is an important function for biocontainment and minimizing unintended environmental impact. By integrating genetically engineered stimuli-responsive cyanobacteria in patterned volumetric 3D-printed designs, we demonstrate the potential of programmable photosynthetic biocomposite materials capable of producing functional outputs including, but not limited to, bioremediation.
Age and Ageing · 2023-09-01
articleSenior authorAbstract Background Supporting people with dementia to live at home in their communities post-diagnosis is a goal of national and international policy. Local area-based, community driven services can play a key role in supporting people with dementia post-diagnosis, and have demonstrated their role in helping to move the existing care system to a personalised model. Sustaining such services over the long-term can be a struggle. This study aimed to understand the factors affecting the sustainability of dementia post-diagnostic support services, how these can best be addressed, and what are the lessons for policymakers and others. Methods This mixed-methods study of one area-based, community driven dementia post-diagnostic service was conducted between September 2022 and February 2023. Qualitative methods were used to explore the perspectives of 47 study participants on the value of the service and its sustainability. The study included focus groups (n = 2) with service staff, interviews with people with dementia (n = 8), family carers (n = 16) and national and locally-based stakeholders (n = 16), and a review of seven years of service activity and expenditure data. Results The study found that the service was widely regarded as a valuable addition to the dementia care landscape, in high demand, well integrated into the service landscape and an important resource for other services. A range of factors were found to affect service sustainability including funding levels, resource allocation mechanisms, working relationships between key organisations, managerial change, organisational restructuring, staff capacity and strategic planning. Conclusion Despite demonstrated value to dementia care landscape, service sustainability cannot be taken for granted. Strategies that will help sustain dementia post-diagnostic services in the long-term need to be adopted. The results will be of interest to policy-makers and a range of other actors involved in planning, implementing and supporting post-diagnostic services as well as service users and healthcare professionals.
Phenotypically complex living materials containing engineered cyanobacteria
Nature Communications · 2023 · 66 citations
- Computational biology
- Biology
- Genetics
The field of engineered living materials lies at the intersection of materials science and synthetic biology with the aim of developing materials that can sense and respond to the environment. In this study, we use 3D printing to fabricate a cyanobacterial biocomposite material capable of producing multiple functional outputs in response to an external chemical stimulus and demonstrate the advantages of utilizing additive manufacturing techniques in controlling the shape of the fabricated photosynthetic material. As an initial proof-of-concept, a synthetic riboswitch is used to regulate the expression of a yellow fluorescent protein reporter in Synechococcus elongatus PCC 7942 within a hydrogel matrix. Subsequently, a strain of S. elongatus is engineered to produce an oxidative laccase enzyme; when printed within a hydrogel matrix the responsive biomaterial can decolorize a common textile dye pollutant, indigo carmine, potentially serving as a tool in environmental bioremediation. Finally, cells are engineered for inducible cell death to eliminate their presence once their activity is no longer required, which is an important function for biocontainment and minimizing environmental impact. By integrating genetically engineered stimuli-responsive cyanobacteria in volumetric 3D-printed designs, we demonstrate programmable photosynthetic biocomposite materials capable of producing functional outputs including, but not limited to, bioremediation.
Life Sciences in Space Research · 2022-11-04 · 4 citations
articleOpen accessSenior authorCorrespondingSome designs for bioregenerative life support systems to enable human space missions incorporate cyanobacteria for removal of carbon dioxide, generation of oxygen, and treatment of wastewater, as well as providing a source of nutrition. In this study, we examined the effects of the short light-dark (LD) cycle of low-Earth orbit on algal and cyanobacterial growth, approximating conditions on the International Space Station, which orbits Earth roughly every 90 min. We found that growth of green algae was similar in both normal 12 h light:12 h dark (12 h:12 h LD) and 45':45' LD cycles. Three diverse strains of cyanobacteria were not only capable of growth in short 45':45' LD cycles, but actually grew better than in 12 h:12 h LD cycles. We showed that 45':45' LD cycles do not affect the endogenous 24 h circadian rhythms of Synechococcus elongatus. Using a dense library of randomly barcoded transposon mutants, we identified genes whose loss is detrimental for the growth of S. elongatus under 45':45' LD cycles. These include several genes involved in glycogen metabolism and the oxidative pentose phosphate pathway. Notably, 45':45' LD cycles did not affect the fitness of strains that carry mutations in the biological circadian oscillator or the clock input and output regulatory pathways. Overall, this study shows that cultures of cyanobacteria could be grown under natural sunlight of low-Earth orbit and highlights the utility of a functional genomic study in a model organism to better understand key biological processes in conditions that are relevant to space travel.
Altered Carbon Partitioning Enhances CO2 to Terpene Conversion in Cyanobacteria
BioDesign Research · 2022-01-01 · 17 citations
articleOpen accessPhotosynthetic terpene production represents one of the most carbon and energy-efficient routes for converting CO2 into hydrocarbon. In photosynthetic organisms, metabolic engineering has led to limited success in enhancing terpene productivity, partially due to the low carbon partitioning. In this study, we employed systems biology analysis to reveal the strong competition for carbon substrates between primary metabolism (e.g., sucrose, glycogen, and protein synthesis) and terpene biosynthesis in Synechococcus elongatus PCC 7942. We then engineered key “source” and “sink” enzymes. The “source” limitation was overcome by knocking out either sucrose or glycogen biosynthesis to significantly enhance limonene production via altered carbon partitioning. Moreover, a fusion enzyme complex with geranyl diphosphate synthase (GPPS) and limonene synthase (LS) was designed to further improve pathway kinetics and substrate channeling. The synergy between “source” and “sink” achieved a limonene titer of 21.0 mg/L. Overall, the study demonstrates that balancing carbon flux between primary and secondary metabolism can be an effective approach to enhance terpene bioproduction in cyanobacteria. The design of “source” and “sink” synergy has significant potential in improving natural product yield in photosynthetic species.
ACS Chemical Biology · 2022-06-27 · 15 citations
articleOpen accessSenior authorCorrespondingColumbamides are chlorinated acyl amide natural products, several of which exhibit cannabinomimetic activity. These compounds were originally discovered from a culture of the filamentous marine cyanobacterium Moorena bouillonii PNG5-198 collected from the coastal waters of Papua New Guinea. The columbamide biosynthetic gene cluster (BGC) had been identified using bioinformatics, but not confirmed by experimental evidence. Here, we report the heterologous expression in Anabaena (Nostoc) PCC 7120 of the 28.5 kb BGC that encodes for columbamide biosynthesis. The production of columbamides in Anabaena is investigated under several different culture conditions, and several new columbamide analogs are identified by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and nuclear magnetic resonance (NMR). In addition to previously characterized columbamides A, B, and C, new columbamides I–M are produced in these experiments, and the structure of the most abundant monochlorinated analog, columbamide K (11), is fully characterized. The other new columbamide analogs are produced in only small quantities, and structures are proposed based on high-resolution-MS, MS/MS, and 1H NMR data. Overexpression of the pathway’s predicted halogenases resulted in increased productions of di- and trichlorinated compounds. The most significant change in production of columbamides in Anabaena is correlated with the concentration of NaCl in the medium.
Recent grants
NIH · $1.2M · 2021
Regulation of Genes Required for Nitrogen Fixation in Anabaena Heterocysts
NSF · $424k · 2008–2012
NSF · $427k · 2018–2023
NIH · $4.3M · 2008
Frequent coauthors
- 18 shared
Arnaud Taton
University of California, San Diego
- 10 shared
Susan S. Golden
University of California, San Diego
- 10 shared
Claudio D. Carrasco
Thermo Fisher Scientific (United States)
- 8 shared
T. Ramasubramanian
- 8 shared
Robert Haselkorn
University of Chicago
- 7 shared
Raphael Reher
Philipps University of Marburg
- 7 shared
Rodrigo A. Mella-Herrera
Universidad de La Frontera
- 6 shared
Ho‐Sung Yoon
Kyungpook National University
Education
- 1983
Ph. D., Biology
University of Missouri Columbia
- 1977
B. S., Microbiology
University of Maryland
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