FEMS Microbiology Ecology, 97, 2021, fiaa249

doi: 10.1093/femsec/fiaa249 Advance Access Publication Date: 4 December 2020 Minireview

MINIREVIEW

Synthetic biology approaches to copper remediation: Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 bioleaching, accumulation and recycling Andrea Giachino1,†, Francesca Focarelli1, Jon Marles-Wright2 and Kevin J. Waldron1,*,‡

1Faculty of Medical Sciences, Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom and 2School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom

∗Corresponding author: Faculty of Medical Sciences, Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom. Tel: (+44) 191 208 7036; E-mail: [email protected] One sentence summary: A review of current technologies in bacterial bioremediation, biorecycling and bioleaching, of copper homeostasis strategies used by bacteria, and how these could be exploited through synthetic biology for bioremediation. Editor: Marcus Horn †Andrea Giachino, http://orcid.org/0000-0002-7725-1065 ‡Kevin J. Waldron, http://orcid.org/0000-0002-5577-7357

ABSTRACT One of the current aims of synthetic biology is the development of novel microorganisms that can mine economically important elements from the environment or remediate toxic waste compounds. Copper, in particular, is a high-priority target for bioremediation owing to its extensive use in the food, metal and electronic industries and its resulting common presence as an environmental pollutant. Even though microbe-aided copper biomining is a mature technology, its application to waste treatment and remediation of contaminated sites still requires further research and development. Crucially, any engineered copper-remediating chassis must survive in copper-rich environments and adapt to copper toxicity; they also require bespoke adaptations to specifically extract copper and safely accumulate itasa human-recoverable deposit to enable biorecycling. Here, we review current strategies in copper bioremediation, biomining and biorecycling, as well as strategies that extant bacteria use to enhance copper tolerance, accumulation and mineralization in the native environment. By describing the existing toolbox of copper homeostasis proteins from naturally occurring bacteria, we show how these modular systems can be exploited through synthetic biology to enhance the properties of engineered microbes for biotechnological copper recovery applications.

Keywords: copper; bioremediation; synthetic biology; bacteria; copper homeostasis

INTRODUCTION (AMR; Grass, Rensing and Solioz 2011; Michels et al. 2015;Vin- cent, Hartemann and Engels-Deutsch 2016; Warnes and Keevil Copper (Cu) is a key metal resource for human activities. It is 2016). Copper nanoparticles (CuNP), in particular, are important used in applications as diverse as electronics, agriculture, farm- antimicrobials (Ruparelia et al. 2008;Liet al. 2013a; Lalitha et al. ing, brewing and winemaking and the wood industry (Cornu 2020) and chemical catalysts (Ressler et al. 2005; Vukojevic´ et al. et al. 2017). Moreover, the antibacterial properties of copper are 2005; Kimber et al. 2018; Tountas et al. 2019). used in healthcare as an alternative to antibiotic treatments, Each year, approximately 20 million metric tonnes of copper with the aim of tackling increasing antimicrobial resistance are mined worldwide (U.S. Geological Survey 2020), and most of

Received: 4 August 2020; Accepted: 2 December 2020

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1 2 FEMS Microbiology Ecology, 2021, Vol. 97, No. 2

the copper entering the economy is lost at the end of its primary 2017; Rawlings 2002;Carranzaet al. 2009; Potysz et al. 2015; lifecycle. In the USA, only 35% of the 2019 copper supply was Zepeda et al. 2017). contributed by recovered copper scraps, the majority of which Recently, studies focusing on biorecycling of copper (and came from the pre-consumer stage (U.S. Geological Survey 2020). other metals) have yielded promising results (reviewed in Poll- Copper is also released into the environment by mining activi- mann et al. (2018)). Copper biorecovery from electrical and elec- ties, farming and agriculture (Poulsen 1998; Nicholson et al. 2003; tronic waste seems particularly favorable, as these types of Wilson and Pyatt 2007;Wightwicket al. 2008; Gillan et al. 2017; waste contain amounts of copper comparable to ores from tra- Lamichhane et al. 2018), and the issue of copper contamination is ditional mines, or even higher (Thakur and Kumar 2020). A particularly pressing in low-income countries (Wong et al. 2007; Strengths, Weaknesses, Opportunities and Threats (SWOT) anal- Liu et al. 2015;Singhet al. 2020). Remediation of copper pollu- ysis, published this year by Gomes, Funari and Ferrari (2020), tion will contribute to a number of the UN Sustainable Devel- identified ashes from municipal waste incineration as a suitable opment Goals, in particular Goal 6: Clean Water and Sanita- target for commercial copper recovery via bioleaching. Other tion; and Goal 9: Industry Innovation and Infrastructure (United reviews extensively addressed recent advances in the biomin- Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 Nations General Assembly 2015). In addition, waste copper con- ing of complex metal waste, including copper (Pollmann et al. stitutes a growing above-ground resource, which could poten- 2018; Sethurajan, van Hullebusch and Nancharaiah 2018;Auer- tially complement mineral resources as high quality geological bach et al. 2019; Srichandan et al. 2019). However, the current deposits become depleted (Dunbar 2017). technology readiness level (TRL) for bioremediation and biorecy- Agricultural lands, soil and marine environment are espe- cling of copper-containing waste is still low (Gomes, Funari and cially threatened by copper pollution since this metal is a pow- Ferrari 2020), partially owing to current low mining costs and erful pollutant even at moderate concentrations (Rehman et al. cheap landfill disposal (Gomes, Funari and Ferrari 2020). This is 2019;Singhet al. 2020). However, what constitutes a ‘safe’ level expected to change rapidly in the future (Dunbar 2017), as biore- of copper concentration is currently unclear. The World Health mediation of contaminated sites becomes more pressing. Organization guidelines define 2 mg/L as the safe upper limit for One crucial challenge in copper recovery is the toxic nature of total dissolved copper levels in water (WHO 1993, 2004). How- this ion. Most biomining and bioremediating strains are selected ever, the natural copper content in soil is hugely variable, rang- from environmental samples that survive in copper-rich envi- ing from tens to thousands of mg Cu/kg depending on local geol- ronments (Orell et al. 2010); and in the case of biomining, a well- ogy and anthropogenic activities (Cornu et al. 2017; Gillan et al. established suite of methods is available to recover, test and 2017; Rehman et al. 2019). Freshwater and marine ecosystems select bioleaching organisms (Schippers 2007;Orellet al. 2010; are similarly variable, and may experience seasonal fluctuations Gumulya et al. 2018; Pourhossein and Mousavi 2018). On the in the range of μg–mg/L (Miller et al. 1966; Boyle, Huested and other hand, the use of synthetic biology in copper recovery is a Jones 1981; Kremling and Hydes 1988; Nagorski, McKinnon and relatively recent concept (Capeness and Horsfall 2020). Nonethe- Moore 2003; Belabed et al. 2017). less, some synthetic biology applications have been explored As environmental copper concentrations are highly variable, for biomining (Dunbar 2017; Gumulya et al. 2018) and post- so is the copper tolerance of local microorganisms. The majority production remediation (Capeness and Horsfall 2020). Develop- of bacteria require only trace quantities of copper to metalate ments in this field face technical challenges, and also the eth- their copper-dependent enzymes (Festa and Thiele 2011), and ical and legal issues created by the potential for environmen- can efficiently scavenge this essential nutrient. Those organisms tal release of genetically modified organisms (Das, Dash and that feature unusually high copper demands, such as methan- Chakraborty 2016). otrophic bacteria, have evolved to increase the affinity of their In this review, we summarize existing applications of bio- copper acquisition systems rather than migrate to copper-rich logical systems for bioremediation, bioleaching and biomining. environments (El Ghazouani et al. 2012). Indeed, most bacteria, We then describe the advantages of genetically modified bac- including common pathogens, are sensitive to copper at μMlev- teria for these applications and review the available toolkit for els (Rensing and Grass 2003; Tottey et al. 2012;Tarrantet al. 2019). copper-related synthetic biology in bacteria. This includes bac- These microbes, however, can evolve to tolerate copper concen- terial strains, copper-handling pathways and copper biosensors trations that are orders of magnitude higher, typically through that can be exploited to detect, capture and re-utilize copper duplication of copper resistance genes or horizontal transfer of from different environments. We show how these tools could novel ones (von Rozycki and Nies 2009; Gillan et al. 2017;Liet al. be combined in a modular way to achieve different bioengineer- 2020; Palanivel et al. 2020). In some cases, evolutionary selec- ing goals, and how to adapt them to different growth and envi- tion for copper resistance has been shown to favour the spread ronmental conditions. By highlighting the potential for future of other AMR determinants via linked inheritance (reviewed in exploitation of both extant bacteria and of synthetic microbes Baker-Austin et al. (2006)). in bioremediation applications, as well as the technical and reg- Bioremediation, the use of living organisms to ‘clean up’ a ulatory challenges that must be overcome, we intend to stimu- contaminated environment, is a promising field for waste treat- late further research to understand the molecular functions of ment as it offers a potentially cheaper, more effective and more these bacterial copper-handling proteins and to develop them ecologically friendly method of waste decontamination than into functional bioengineering modules. current chemical treatments. These benefits could be increased further if bioremediation efforts can be combined with methods COPPER BIOLOGICAL CHEMISTRY of recovery to yield a biorecycling process (Kaksonen et al. 2011; Pollmann et al. 2018; Capeness and Horsfall 2020). Crucially, bio- In most cases, copper occurs in one of three oxidation states. logical copper recovery is already a fully-developed technology Elemental copper, Cu(0), is the solid form of the metal which in the mining industry (Brierley 2016; Latorre et al. 2016), with is used in metallurgy. It is the form with the highest economic copper biomining from low-grade ores, mining dumps and met- value, and ideally the end point of any (bio)metallurgical pro- allurgical slags contributing an estimated 15–20% of the total cess. Even though copper surfaces show important antimicro- mined copper worldwide (Brierley 2016;Kaksonenet al. 2011, bial properties (Casey et al. 2010; Coppin et al. 2017;Inkinen Giachino et al. 3

et al. 2017), Cu(0) is not readily soluble. As a consequence, free- Despite their sensitivity to copper, bacteria are important swimming microbes are largely unaffected by Cu(0), and biore- players in ecological copper cycles (Knapp et al. 2007;Gadd2010; duction/precipitation of ionic copper to its metallic form is a DiSpirito et al. 2016;Posackaet al. 2017). They can also adapt convenient way to recover it from contaminated solutions. quickly to copper-rich environments by acquiring additional As we have discussed elsewhere (Barwinska-Sendra and copper-resistance genes (von Rozycki and Nies 2009; Gillan et al. Waldron 2017), soluble, ionic copper exists as a dynamic equi- 2017;Liet al. 2020). Horizontal transfer of copper homeostasis librium between two oxidation states: cuprous Cu(I) and cupric genes is especially frequent in the animal microbiome (Qin et al. Cu(II). The relative equilibrium between these species depends 2014;Fanget al. 2016; Chalmers et al. 2018), and can increase bac- on the solvent’s oxic state and the presence of competitive lig- terial resilience to immune system killing (Planet et al. 2015;Fang ands, and is therefore highly variable. Notably, different biologi- et al. 2016; Billman-Jacobe et al. 2018; Purves et al. 2018; Zapo- cal compartments may favor one species compared to the other: toczna et al. 2018), as well as promoting the co-inheritance of the cytosol (a reductive environment) is known to favor the con- other plasmid- or transposon-borne AMR islands (Baker-Austin version of Cu(II) to Cu(I), while oxidizing compartments such as et al. 2006). Thus, appropriate remediation of copper waste Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 the periplasm of Gram-negative bacteria favor Cu(II) (Giachino would not only safeguard contaminated environments, but also and Waldron 2020). reduce the spread of multidrug-resistant pathogens. Despite a long history of clinical exploitation of copper’s antimicrobial properties (Dollwet and Sorenson 1985), its pre- cise role in biology has only been elucidated in the last four CURRENT APPROACHES TO BIOLEACHING decades. As a micronutrient, copper is essential for cuproen- zymes involved in core metabolic processes such as respira- Even though commercial applications of copper biomining have tion and photosynthesis, in redox reactions, and as a structural long been established (Johnson 2013), copper bioremediation cofactor (Andreini et al. 2008; Decaria, Bertini and Williams 2011; from post-production environments, as well as historical sites, Festa and Thiele 2011; Ross et al. 2019; Stewart et al. 2019). At the is a much more recent development (Potysz and Kierczak 2019). same time, the vast majority of extant organisms have evolved The most widespread method for copper biomining is bioleach- complex copper handling machineries to deal with excess cop- ing: the extraction of soluble copper from complex solid mix- per (Andreini et al. 2008; Decaria, Bertini and Williams 2011; tures (Gumulya et al. 2018). Therefore, it is not surprising that Giachino and Waldron 2020). bioleaching has been the focus of recent approaches to copper Generally, the cuprous ion, Cu(I), is the most toxic to microor- bioremediation (Fonti, Dell’Anno and Beolchini 2016)andrecy- ganisms, especially bacteria (Rensing and Grass 2003;Andreini cling (Drob´ıkova´ et al. 2015). et al. 2008). The pleiotropic effects of Cu(I) toxicity arise from Successful applications of copper bioleaching for reme- cofactor displacement from metalloenzymes, steric inhibition of diation include the use of the chemolithotrophic bacterium substrate-binding sites and alterations of the cell’s redox cycles Acidithiobacillus ferrooxidans to recover copper from dry discarded (Macomber and Imlay 2009;DjokoandMcEwan2013; Giachino incineration slags (Auerbach et al. 2019) and fly ashes (Ishigaki and Waldron 2020). Moreover, Cu(I) is more mobile than Cu(II), et al. 2005; Funari et al. 2017; Meer and Nazir 2018). This method being able to cross biological membranes through various trans- is less resource-consuming than chemical leaching (Funari et al. porters (Al-Tameemi et al. 2020). As a consequence, many cells 2017), and can access finer particle sizes than other recycling possess endogenous systems to excrete Cu(I) or oxidize it to methods (Auerbach et al. 2019). Additionally, copper has been Cu(II), typically using oxygen as an electron acceptor. Alterna- successfully bioleached from smelting sludges (Guo et al. 2010; tively, cells may precipitate copper by adsorbing it to copper- Ilyas et al. 2013; Klink et al. 2016), activated sludge from wastew- binding proteins (Rosario-Cruz et al. 2019), or extracellularly ater treatment (Meulepas et al. 2015) and shredded electronic through the secretion of copper chelators (Gold et al. 2008;Liet al. waste (Brandl, Bosshard and Wegmann 2001; Faramarzi et al. 2020; Palanivel et al. 2020). Other pathways take care of intra- 2004;Wanget al. 2009, 2016; Chi et al. 2011;Zhuet al. 2011; Xia cellular copper management (Vita et al. 2015, 2016), monitoring et al. 2017). (Outten et al. 2001; Giachino and Waldron 2020)anddeliveryto After its extraction from waste, soluble copper can be recov- cuproenzymes (Robinson and Winge 2010; Stewart et al. 2019). ered from the leachate in various ways (Pollmann et al. 2018), As mentioned before, bacteria are especially sensitive to cop- including biosorption, bioflotation, bioreduction, bioelectro- per toxicity. Because their evolution predates the liberation of chemistry, biomineralization and bioprecipitation (Nanchara- soluble copper in Earth’s biosphere (Williams 2007), they gen- iah, Venkata Mohan and Lens 2015; Modin and Aulenta 2017; erally have lower copper requirements than eukaryotes. Their Li, Cheng and Guo 2013b). Among these, the most studied high surface-to-volume ratio, and the lack of membrane-bound approaches are biosorption and bioprecipitation. organelles to protect vulnerable cellular components, make In biosorption, inert biomass or biomolecules are used to them even more exposed to copper toxicity. This sensitivity ‘soak up’ a contaminant from solution (Volesky 2007); this underpins copper usage as a pesticide in agriculture (Wightwick approach is particularly effective for copper, since this metal et al. 2008; Lamichhane et al. 2018) and as an antimicrobial in has very high affinity for biological ligands (Ghaed, Shirazi and the clinic (Casey et al. 2010; Michels et al. 2015; Lamichhane et al. Marandi 2013). The most recent biosorption approaches utilize 2018). Moreover, the mammalian immune system utilizes cop- peptide-functionalized membranes (Urbina et al. 2019)andbio- per in its antimicrobial arsenal to fend off invading pathogens logical ceramic composites (Raff et al. 2003;Wanget al. 2016)to (White et al. 2009;Achardet al. 2010; Ladomersky et al. 2017), achieve high affinity and specificity. However, the contaminated which may contribute to improved health and increased growth adsorbent is often an end-product, and must be burned or oth- in copper-supplemented animals (Poulsen 1998). In fact, copper erwise disposed of after bioremediation (Yang et al. 2020). tolerance is important for the virulence of numerous pathogenic Bioprecipitation is a technique used in biomining to recover bacteria, including Mycobacterium tuberculosis, Salmonella enterica copper from low-grade ores and mine flotation tailings (Zepeda and Streptococcus pneumoniae (Achard et al. 2010; Wolschendorf et al. 2017). Compared to biosorption, bioprecipitation requires et al. 2011; Johnson et al. 2015; Ladomersky et al. 2017). the use of living bacteria and dedicated culture systems; on 4 FEMS Microbiology Ecology, 2021, Vol. 97, No. 2

the other hand, it produces no waste end-product. Bioprecip- and Yoon 2019; Tapscott, Guarnieri and Henard 2019) enabling itation has been used successfully to remove contaminating the production of added-value compounds from methane (Can- copper from dredged sediment (Fang et al. 2011)aswellas tera et al. 2019). swine wastewater and cheese production wastewater (Hawari An alternative strategy to bioremediation is the use of and Mulligan 2006;Zenget al. 2021). Bioprecipitation can fur- well-established heterotrophic chassis to deploy the copper- ther be enhanced by using strains that secrete copper-chelating remediation pathway (Gumulya et al. 2018; Calero and Nikel exopolysaccharides (Gupta and Diwan 2017), or accumulate cop- 2019), including well-known E. coli, Bacillus subtilis and Pseu- per intracellularly or on the cell surface (Ni et al. 2012; Giner- domonas strains (Pardo et al. 2003; Chen et al. 2005; Tunali, C¸abuk Lamia, Lopez-Maury´ and Florencio 2015). and Akar 2006; Uslu and Tanyol 2006; Vullo et al. 2008;Niet al. 2012; Potysz et al. 2016a; Choi et al. 2018). The genus Pseudomonas, in particular, can extract copper with high affinity thanks to BACTERIAL CHASSIS FOR COPPER its natural secretion of siderophores and chalkophores (Cornu REMEDIATION et al. 2017). In addition, the genera Morganella and Shewanella Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 have also been explored due to their natural production of cop- So far, a wide variety of bacterial species have been used for per nanoparticles (CuNP), which occurs extracellularly in Mor- bioremediation (Nakajima et al. 2001; Ozt¨ urk,¨ Artan and Ayar ganella (Ramanathan et al. 2013; Pantidos, Edmundson and Hors- 2004;Albarrac´ın, Amoroso and Abate 2005; Beolchini et al. 2006; fall 2018; Lalitha et al. 2020) and intracellularly in Shewanella Lu et al. 2006; Achal, Pan and Zhang 2011; Oves, Khan and Zaidi (Kimber et al. 2018). Recently, CuNP production has been het- 2013; Veneu, Torem and Pino 2013; Mejias Carpio et al. 2014; Lac- erologously introduced in E. coli (Choi et al. 2018), demonstrating erda et al. 2019;Zenget al. 2021). These can be broadly divided the potential for facile transfer of copper-bioremediating prop- according to their growth requirements, between autotrophic erties across bacterial species. A comprehensive review of rele- bacteria (including extremophiles and cyanobacteria) and het- vant genes for copper biomining and remediation can be found erotrophic bacteria (including genetically modified model sys- in Orell et al. (2010). tems such as Escherichia coli). Genetically modified organisms, whether auto- or hetero- Autotrophic bacteria (methanotrophs, lithotrophs and trophic, present significant advantages over those selected by cyanobacteria) have a number of advantages over heterotrophic directed evolution, including the possibility to be tailored for species (Cornu et al. 2017). Firstly, they normally possess ded- higher specificity and lower costs, and to be readily re-adapted icated pathways for copper acquisition and storage, which to different application areas (Capeness and Horsfall 2020). facilitates chassis design. Secondly, they normally require rela- However, they also present distinctive challenges. Traditional tively little external nutrient input, reducing their application bioleaching cultures are typically isolated from natural systems, costs. It is therefore not surprising that the most common and are therefore anticipated to pose fewer risks to humans or chassis for bioleaching, Acidithiobacillus, is a lithoautotroph the environment (Gomes, Funari and Ferrari 2020). On the other (Valdes´ et al. 2008;Vestolaet al. 2010; Potysz et al. 2016b). hand, the application of genetically modified or synthetic organ- Cyanobacteria are also used for bioremediation (Mohapatra isms must be consistent with the regulatory environment in the and Gupta 2005; El-Bestawy 2008) as they possess dedicated jurisdiction in which they are to be deployed, with consideration pathways for copper delivery to their copper-rich thylakoids given to adequate containment measures and specific legislative (Huertas et al. 2014). Finally, methanotrophs in the Methylo- frameworks (European Parliament and Council 2001;UKParlia- genera (such as Methylosinus and Methylocystis) are important ment 2002; EC Scientific Committees 2015). Such challenges are copper accumulators (Strong, Xie and Clarke 2015), as they common to all synthetic biology applications (Hewett et al. 2016; store copper in intracellular compartments for utilization by Wang and Zhang 2019), with almost all applications involving copper-dependent methane oxygenases (Brantner et al. 2002; genetically modified bacteria taking place in contained environ- Strong, Xie and Clarke 2015;Vitaet al. 2015). ments. The release of genetically modified plants is particularly Another attractive feature of autotrophic bacteria is their contentious in the European Economic Area, whereas geneti- capability to synthesise added-value compounds from waste cally modified crops are widely cultivated in other parts ofthe carbon sources. Both cyanobacteria (Al-Haj et al. 2016;Jimenez-´ world, including the United States, India and China. D´ıaz et al. 2017;Khanet al. 2019) and methanotrophs (Cantera One factor that must be considered for the development of et al. 2019) have already been used for this purpose. Methan- novel chassis is the environment in which they will be used. ‘Kill otrophs, in particular, have been explored for their potential to switches’ and designed auxotrophies have been widely stud- remediate methane (a powerful greenhouse gas) at the same ied as containment strategies to enable the release of remedi- time as they remediate copper (Strong, Xie and Clarke 2015). ating organisms in the polluted environment (Simon and Elling- Despite their many advantages, the adoption of autotrophs ton 2016). Similarly, the potential for lateral transfer of copper- in bioremediation is currently limited. Lithotrophs, in particular, resistance genes from the synthetic microbe to native organ- are not amenable to genetic engineering at present (Gumulya isms must also be considered and, if possible, prevented, given et al. 2018; Capeness and Horsfall 2020), meaning that strain the obvious selection pressures present in copper-contaminated improvement can only be achieved via directed evolution (Feng, sites (Li et al. 2020). Conversely, synthetic microbes must be Yang and Wang 2015; Pourhossein and Mousavi 2018). More- designed to ensure that the genetic arsenal is retained by the over, they often require extremely acidic growth environments, bacterium throughout the duration of the remediation event, which are incompatible with alkaline wastes (Gomes, Funari and in order to ensure that the accumulated copper is retained and Ferrari 2020). Better-established genetic tools are available for prevent loss of bioremediation and biorecycling capacity until cyanobacteria (Gale et al. 2019), which offer several strains opti- metal recovery can be achieved. Yet, current biosecurity con- mized for growth performance (Gale et al. 2019) and metabolic cerns and regulatory barriers make it unlikely that a freely- engineering (Calero and Nikel 2019). The use of methanotrophs released bioremediating organism could be deployed in the fore- for synthetic biology is also gaining momentum, with novel seeable future (see Bereza-Malcolm, Mann and Franks (2015)for strains and genetic tools (Ro and Rosenzweig 2018;Kwon,Ho extensive discussion). Fully contained systems, similar to those Giachino et al. 5

already employed in the biomining industry, are more likely to native organism, repressing copper uptake when the intracellu- be considered acceptable under current legislation, as well as lar buffering capacity is overloaded (Hirooka et al. 2012). Nega- promoting science-driven changes in the regulatory landscape. tive repressible promoters can be used as ‘safety valves’ to pre- When this happens, having developed market-ready applica- vent the cytotoxic effects of excess copper, as well as to repress tions will constitute a significant competitive advantage. growth-related genes during the copper bioremediation phase. The last sub-group of copper-responsive promoters are those of the negatively inducible type, which are repressed by their COPPER BIOSENSORS regulator, but turn back on upon copper addition. They consti- tute the most diverse class, including proteins that can respond In most cases, detecting a target contaminant is the first step to Cu(I) (CopY and ComR; Mermod et al. 2012; O’Brien et al. 2020), in bioremediation (Ravikumar et al. 2017; Capeness and Hors- Cu(II) (GfcR; Rao et al. 2012; Suvorova, Korostelev and Gelfand fall 2020). Whole-cell microbial bioreporters are a simple and 2015), or both (CsoR; Sakamoto et al. 2010). inexpensive method to detect the presence of a contaminant, In addition to their simple applications in whole-cell biosen- Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 usually giving indications on its concentration (Bereza-Malcolm, sors (Ravikumar et al. 2012), copper-responsive regulons can be Mann and Franks 2015; Kim, Jeong and Lee 2018). Moreover, combined into complex syntaxes (Wang, Barahona and Buck contaminant-responsive transcriptional regulators can reduce 2013;Singh2014; Bradley and Wang 2015). Positive inducible a chassis’ maintenance cost by ensuring that cellular resources systems can be chained for signal amplification, or to integrate are only directed to the engineered arsenal when in contact with multiple stimuli as part of AND-type logic gates (Wang, Bara- the target contaminant (Zhang and Keasling 2011). They can also hona and Buck 2013; Kim, Jeong and Lee 2018). Negative repress- facilitate dynamic regulation in response to different concentra- ible promoters, on the other hand, are prototypical NAND-type tions of exogenous metal, further optimizing resource allocation gates. Combined with a wide range of copper sensitivities (rang- (McNerney et al. 2015). The state-of-the-art in metal biosens- ing from zeptomolar for CueR to micromolar for CusSR; Franke, ing, including future opportunities and critical bottlenecks, Grass and Nies 2001; Changela et al. 2003; Villafane et al. 2009; has been recently reviewed (Kim, Jeong and Lee 2018). Others Giner-Lamia et al. 2012; Gudipaty and McEvoy 2014), these oper- have discussed metal biosensor acceptability and optimization ons can dynamically fine-tune the response of a bioremedia- (Bereza-Malcolm, Mann and Franks 2015; Jaejoon and Sang Jun tion chassis according to copper availability (Ravikumar et al. 2019), and all of these principles are also applicable to copper 2011; McNerney et al. 2015). An interesting application of copper- biosensors. responsive promoters is the regulation of suicide genes, which A wide range of copper-responsive transcriptional regula- can increase the safety and regulatory compliance of GMO tor systems have been characterized to date (Rademacher and strains by ensuring their self-destruction upon successful reme- Masepohl 2012), and find applications in whole-cell copper diation (Das, Dash and Chakraborty 2016). biosensors (Ravikumar et al. 2012;Liet al. 2014; Martinez, Heil and Charles 2019) and microbial fuel cells (Zhou et al. 2020). COPPER SEQUESTRATION BY WHOLE CELLS Genome mining, directed evolution and mutant screening can further expand the toolkit of available copper sensors (De Paepe Although both Gram-negative and Gram-positive bacteria can et al. 2017; Kim, Jeong and Lee 2018). Importantly, copper- grow robustly while efficiently accumulating copper in the hun- responsive transcriptional regulators are remarkably diverse in dreds of ng Cu/mg biomass (Haeili et al. 2014), the most obvious their copper affinity, cellular localization and modes of reg- bottleneck in copper bioremediation is the high toxicity of cop- ulation of gene expression (Martinez, Heil and Charles 2019; per to bacterial cells (Bereza-Malcolm, Mann and Franks 2015). Fig. 1). When designing a synthetic copper-biosensing, -biomining, or The simplest copper-responsive promoters in bacterial -bioremediating chassis, the introduction of effective copper genomes are positively regulated, requiring both copper and a buffering and accumulating pathways should be a priority specific transcriptional regulator to induce transcription. Well- (Bereza-Malcolm, Mann and Franks 2015). The goal should be characterized regulators in this class include CueR, which to enable the synthetic organisms to accumulate greater quan- senses cytosolic Cu(I) (Changela et al. 2003; Villafane et al. tities of copper than is feasible within extant organisms, with- 2009; Philips et al. 2015), and CorE, which senses cytosolic out inducing copper toxicity. Copper-binding biomolecules are Cu(II) (Gomez-Santos´ et al. 2011;Perez,´ Munoz-Dorado˜ and of special interest in this, as they can also boost copper seques- Moraleda-Munoz˜ 2018). In addition, the CusSR two-component tration and thus contribute to a strain’s remediating potential kinase/regulator system can respond to extracytosolic Cu(I) (Fig. 2). Notably, it has been shown that bacterial copper accumu- (Giner-Lamia et al. 2012;Sanchez-Sutil´ et al. 2016; Affandi lation can be enhanced by expression of copper-binding proteins and McEvoy 2019), providing a more direct readout of the (Ueki et al. 2003; Lee and Dennison 2019;Liet al. 2020), which extracellular environment (Ravikumar et al. 2017); this sys- contribute to copper accumulation whilst at the same time pro- tem has been successfully employed in microbial fuel cell tecting the host chassis from copper toxicity. applications for monitoring copper pollution in aquatic sam- Secreted chalkophores (reviewed in Kenney and Rosenzweig ples (Zhou et al. 2020). Importantly, the sensory domain (2018)), such as Cu(I)-binding methanobactin (Behling et al. 2008; of histidine kinases can be hybridized with non-cognate Balasubramanian, Kenney and Rosenzweig 2011; DiSpirito et al. kinase/phosphatases (Baumgartner et al. 1994), making it possi- 2016), Cu(II)-binding yersiniabactin (Koh et al. 2017), and azurin ble to connect the copper-sensing input with non-native output (Raimunda et al. 2013; Han et al. 2019), can mediate copper leach- modules. ing with femtomolar affinity from extracellular ligands, in addi- At the opposite end of the spectrum are negative repress- tion to its subsequent uptake by the cell (Knapp et al. 2007; Kul- ible promoters, which are always active unless both copper and czycki et al. 2007;Peschet al. 2013). They can also adsorb cop- the regulatory protein are present. This class includes the B. per to cell membranes, in the form of cell surface-immobilized subtilis YcnK, which senses cytosolic Cu(I) (Chillappagari et al. copper-binding molecules (Ravikumar et al. 2011;Niet al. 2012; 2009; Hirooka et al. 2012) and fine-tunes copper acquisition in the Giner-Lamia, Lopez-Maury´ and Florencio 2015;Liet al. 2020). For 6 FEMS Microbiology Ecology, 2021, Vol. 97, No. 2 Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021

Figure 1. Copper regulation in synthetic biology. (A) Diverse copper-responsive regulators have been characterized in natural organisms. Positive inducible operons (top, controlled by CueR, CorE or CusSR) produce a positive output (green boxes) in the presence of both copper (brown circles) and the regulator. Negative repressible operons (centre, controlled by YcnK) produce no output (red boxes) when both copper and the regulator are present. Finally, negative inducible operons (bottom, controlled by CopY, ComR, CsoR or GfcR) are only inactive when the regulator, but not copper, is present. (B) In typical copper-dependent feedback, specific regulator proteins sense the presence of copper in a target cellular compartment. When the copper concentration reaches a certain threshold, changes in gene activation result in reduced influx, increased efflux and increased sequestration or storage in specific cellular copper pools. Positive feedback on thed regulatorisuse to amplify and fine-tune the copper response.

Figure 2. Overview of copper trafficking in bacteria. Copper (brown circles) enters the cell via porins, or active transport through the methanobactin (Mbn)/TonB- dependent transporter (TBDT) system. It can also be sequestered extracellularly by chaperones (CopL) or as extracellular copper nanoparticles (ECCuNP). In the periplasm (light blue), copper can be sequestered in copper storage proteins (Csp1/2), or precipitated as intracellular copper nanoparticles (ICCuNP). In the cytosol (dark blue), copper is chelated by a dedicated chaperone (CopZ) and delivered to copper-rich compartments: the methanotrophic intracellular cytosolic membranes (ICM) for particulate methane monooxygenase (pMMO) or the cyanobacterial thylakoid for plastocyanin (Pc). Some bacteria also contain cytosolic copper storage pro- teins (Csp3) for the same function. Excess copper is excreted back to the periplasm by a P-type ATPase (CopA) and transferred to a periplasmic chaperone (CusF), which can then deliver it to periplasmic cuproproteins (such as multicopper oxidases, MCO) or tripartite efflux pumps (CusCBA) for secretion. Copper sequestering proteins are shown in pink, whereas copper trafficking proteins are shown in green. intracellular storage, the most attractive options are intracel- finer control can be achieved by means of small cuprochaper- lular copper storage proteins (Csps), which chelate Cu(I) with ones (Robinson and Winge 2010), which are typically expressed affinity in the attomolar range (Vita et al. 2016; Lee and Denni- at high levels as early copper sinks in response to copper shock son 2019) and can be targeted to different sub-cellular compart- (Rouch and Brown 1997; Lee et al. 2002; Borrelly et al. 2004; Egler ments (Vita et al. 2015, 2016). Intracellular compartments, such et al. 2005;Banciet al. 2010; Osman et al. 2010; Purves et al. as the cyanobacterial thylakoid and the intracytoplasmic mem- 2018). These chaperones contribute to minimize copper toxicity branes of methanotrophs, are also natural candidates for copper by preventing its release in the intracellular milieu (Barwinska- storage (Brantner et al. 2002; Huertas et al. 2014; Whiddon et al. Sendra and Waldron 2017) and facilitating its transport in the 2019). copper-trafficking network (Cha and Cooksey 1993; Zimmer- In most cases, the heterologous expression of individual cop- mann et al. 2012;Fuet al. 2013; Stewart et al. 2019). Impor- per chelators is often sufficient to enhance copper-accumulation tantly, these chaperones can deliver copper to cuproenzymes (Lee and Dennison 2019; Purac´ et al. 2019;Liet al. 2020). An even (Swem et al. 2005; Frangipani and Haas 2009;Thompsonet al. Giachino et al. 7

2010; Waldron et al. 2010;Raimundaet al. 2011; Osman et al. synthetic biology. To effectively accumulate and decontaminate 2012), Csps (Straw et al. 2018), or subcellular compartments such environmental copper, a bespoke synthesis of known copper as the cyanobacterial thylakoid (Huertas et al. 2014). They can sensing, storing, trafficking, utilising and detoxifying proteins also interact with copper-translocating ATPases (Sharma and will be invaluable, especially if coupled with a robust chassis that Rosato 2009; Khalfaoui-Hassani et al. 2010; Osman et al. 2012; can survive and adapt to the harsh conditions in contaminated Azzouzi et al. 2013), which transport Cu(I) with attomolar affinity environments. (Drees et al. 2015) and constitute a varied toolkit with different An inherent advantage of copper-decontaminating organ- kinetic and thermodynamic properties (Arguello¨ 2003; Gonzalez-´ isms is that they can concomitantly act as biorefineries, extract- Guerrero et al. 2010;Raimundaet al. 2011). ing the metal and producing useable secondary copper prod- The most interesting group of cuprochaperones is the ucts. Copper nanoparticles, for example, can be used to recy- periplasmic CopC/PcoC family, which includes members that cle finite copper reservoirs for future medical and electronics can bind Cu(I), Cu(II) or both (Huffman et al. 2002; Wernimont applications (Vukojevic´ et al. 2005; Kimber et al. 2019; Lalitha et al. 2003; Udagedara et al. 2019). In addition to featuring a wide et al. 2020). Furthermore, synthetic organisms would potentially Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 range of copper affinities (Peariso et al. 2003;Lawtonet al. 2016; be able to utilize the accumulated copper for additional benefi- Morosov et al. 2018), these proteins can be engineered to fine- cial functions, such as the consumption of methane and other tune their affinity to either or both ionic forms (Zhang et al. 2006; organic contaminants, as well as the synthesis of useful chem- Wijekoon et al. 2015). The cuprochaperone toolkit also includes icals for human use (Wendlandt et al. 2010; Strong, Xie and the cytosolic CopZ (Cobine et al. 1999, 2002;Banciet al. 2001; Clarke 2015;Canteraet al. 2019; Kwon, Ho and Yoon 2019). An Sharma and Rosato 2009; Chaplin et al. 2015; Novoa-Aponte, additional advantage could be to exploit chemotaxis, enabling Ram´ırez and Arguello¨ 2019) and CupA (Fu et al. 2013, 2016), the the synthetic bioremediating microbes to seek out the contami- periplasmic CusF (Egler et al. 2005; Kittleson et al. 2006;Bagaiet al. nant in the field. Using natural homeostatic systems from extant 2008; Mealman et al. 2011; Chacon´ et al. 2014; Padilla-Benavides organisms and optimising these building blocks for use within et al. 2014) and CueP (Pontel and Soncini 2009; Osman et al. 2012; an integrated heterologous chassis, will be pivotal in assembling Subedi et al. 2019), and the extracellular, membrane-associated bespoke synthetic organisms for the circular economy of a sus- CopL (Purves et al. 2018; Rosario-Cruz et al. 2019). These latter tainable future. chaperones are specific for Cu(I), with affinities in the attomo- In common with other applications of synthetic biology, due lar range for cytosolic and extracellular chaperones (Drees et al. caution and consideration must be given to the potential haz- 2015; Rosario-Cruz et al. 2019), and nanomolar for periplasmic ards associated with the creation, exposure and release of these chaperones (Kittleson et al. 2006). organisms. Adequate containment measures, similar to what are already used in biomining, must be included in bioremedia- CONCLUSIONS AND PERSPECTIVES tion projects from the planning stage. Other strategies to prevent the survival of GM organisms upon accidental release, such as There have been recent expansions of copper-contaminated functional auxotrophies and suicide genes, can also contribute ecological niches, driven primarily by human activities (Nichol- to their safe design; again, there are lessons to be learnt from the son et al. 2003; Wong et al. 2007;Liuet al. 2015; Lamichhane et al. biomining sector, employing extremophile organisms and con- 2018). The exposure of bacteria to excess environmental copper sortia that cannot survive outside of their native environment is therefore on the rise, owing to historical use of copper in agri- culture, both as a fungicide in arable farming and as a growth promoter in pastoral farming, as well as widespread extraction ACKNOWLEDGMENTS and exploitation of copper ores for industrial and technologi- This work was supported by the Biotechnology and Biological cal applications and subsequent disposal of copper-containing Sciences Research Council, UK (grant BB/S006818/1 to KJW and waste (Wong et al. 2007;Liuet al. 2015;Singhet al. 2020). This has grant BB/N005570/1 to JMW). led to the horizontal spread of copper resistance determinants between bacterial genomes, increasing the copper resistance of Conflicts of interest. None declared. strains that acquire such genes (Altimira et al. 2012;Planetet al. 2015;Fanget al. 2016; Billman-Jacobe et al. 2018; Purves et al. 2018; REFERENCES Zapotoczna et al. 2018). Biotechnology offers vast potential for industry, commerce Achal V, Pan X, Zhang D. Remediation of copper-contaminated and medicine, but could also be exploited to assist human soil by Kocuria flava CR1, based on microbially induced calcite efforts to rectify environmental damage, both historical and precipitation. Ecol Eng 2011;37:1601–5. ongoing. Bioremediation of environments that are contami- Achard MES, Tree JJ, Holden JA et al. The multi-copper-ion nated by heavy metals, including copper, can be considered a oxidaseCueOofSalmonella enterica serovar Typhimurium low-hanging fruit in such endeavours, since microorganisms is required for systemic virulence. Infect Immun 2010;78: that hyper-accumulate these metals already exist in the wild 2312–9. (von Rozycki and Nies 2009; Gillan et al. 2017). Microbe-aided Affandi T, McEvoy MM. Mechanism of metal ion-induced copper biomining is a mature and widespread technology (Rawl- activation of a two-component sensor kinase. Biochem J ings 2002;Orellet al. 2010), and adsorption and precipitation 2019;476:115–35. from waste is already feasible in the laboratory. However, further Al-Haj L, Lui YT, Abed RMM et al. Cyanobacteria as chassis for investments will be necessary to advance copper bioremedia- industrial biotechnology: progress and prospects. Life (Basel, tion to higher technology readiness levels (Cornu et al. 2017). Rel- Switzerland) 2016;6:42. atively simple modifications could improve the ability of extant Al-Tameemi H, Beavers WN, Norambuena J et al. Staphylococcus organisms to efficiently clean up metal waste, but in the longer aureus lacking a functional MntABC manganese import sys- term, the development of bespoke biological systems that can tem has increased resistance to copper. Mol Microbiol 2020; perform this task with high efficiency will be a major target of (In press) https://doi.org/10.1111/mmi.14623. 8 FEMS Microbiology Ecology, 2021, Vol. 97, No. 2

Albarrac´ın VH, Amoroso MJ, Abate CM. Isolation and character- Borrelly GPM, Rondet SAM, Tottey S et al. Chimeras of P1-type ization of indigenous copper-resistant actinomycete strains. ATPases and their transcriptional regulators: contributions Geochemistry 2005;65:145–56. of a cytosolic amino-terminal domain to metal specificity. Altimira F, Ya´ nez˜ C, Bravo G et al. Characterization of copper- Mol Microbiol 2004;53:217–27. resistant bacteria and bacterial communities from copper- Boyle EA, Huested SS, Jones SP. On the distribution of copper, polluted agricultural soils of central Chile. BMC Microbiol nickel, and cadmium in the surface waters of the North 2012;12:193. Atlantic and North Pacific Ocean. JGeophysRes1981;86: Andreini C, Bertini I, Cavallaro G et al. Metal ions in biological 8048–66. catalysis: from enzyme databases to general principles. J Biol Bradley RW, Wang B. Designer cell signal processing circuits for Inorg Chem 2008;13:1205–18. biotechnology. N Biotechnol 2015;32:635–43. Arguello¨ JM. Identification of ion-selectivity determinants in Brandl H, Bosshard R, Wegmann M. Computer-munching heavy-metal transport P1B-type ATPases. J Membr Biol microbes: metal leaching from electronic scrap by bacteria

2003;195:93–108. and fungi. Hydrometallurgy 2001;59:319–26. Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 Auerbach R, Ratering S, Bokelmann K et al. Bioleaching of valu- Brantner CA, Remsen CC, Owen HA et al. Intracellular local- able and hazardous metals from dry discharged incineration ization of the particulate methane monooxygenase and slag. An approach for metal recycling and pollutant elimina- methanol dehydrogenase in Methylomicrobium album BG8. tion. J Environ Manage 2019;232:428–37. Arch Microbiol 2002;178:59–64. Azzouzi A, Steunou A-S, Durand A et al. Coproporphyrin III Brierley CL. Biological processing: biological processing of sul- excretion identifies the anaerobic coproporphyrinogen III fidic ores and concentrates—Integrating innovations. In: oxidase HemN as a copper target in the Cu+-ATPase mutant Lakshmanan VI, Roy R, Ramachandran V (eds.) Innova- copA− of Rubrivivax gelatinosus. Mol Microbiol 2013;88:339–51. tive Process Development in Metallurgical Industry: Concept to Bagai I, Rensing C, Blackburn NJ et al. Direct metal transfer Commission. Cham: Springer International Publishing, 2016, between periplasmic proteins identifies a bacterial copper 109–35. chaperone. Biochemistry 2008;47:11408–14. Calero P, Nikel PI. Chasing bacterial chassis for metabolic Baker-Austin C, Wright MS, Stepanauskas R et al. Co-selection engineering: a perspective review from classical to non- of antibiotic and metal resistance. Trends Microbiol 2006;14: traditional microorganisms. Microb Biotechnol 2019;12:98–124. 176–82. Cantera S, Bordel S, Lebrero R et al. Bio-conversion of methane Balasubramanian R, Kenney GE, Rosenzweig AC. Dual pathways into high profit margin compounds: an innovative, environ- for copper uptake by methanotrophic bacteria. J Biol Chem mentally friendly and cost-effective platform for methane 2011;286:37313–9. abatement. World J Microbiol Biotechnol 2019;35:16. Banci L, Bertini I, Ciofi-Baffoni S et al. Affinity gradients drive cop- Capeness MJ, Horsfall LE. Synthetic biology approaches towards per to cellular destinations. Nature 2010;465:645–8. the recycling of metals from the environment. Biochem Soc Banci L, Bertini I, Del Conte R et al. Copper trafficking: the Trans 2020;48:1367–78. solution structure of Bacillus subtilis CopZ. Biochemistry Carranza F, Romero R, Mazuelos A et al. Biorecovery of copper 2001;40:15660–8. from converter slags: slags characterization and exploratory Barwinska-Sendra A, Waldron KJ. The role of intermetal compe- ferric leaching tests. Hydrometallurgy 2009;97:39–45. tition and mis-metalation in metal toxicity. Adv Microb Phys- Casey AL, Adams D, Karpanen TJ et al. Role of copper in iol 2017;70:315–79. reducing hospital environment contamination. JHospInfect Baumgartner JW, Kim C, Brissette RE et al. Transmembrane sig- 2010;74:72–7. nalling by a hybrid protein: communication from the domain Chacon´ KN, Mealman TD, McEvoy MM et al. Tracking metal of chemoreceptor Trg that recognizes sugar-binding proteins ions through a Cu/Ag efflux pump assigns the functional to the kinase/phosphatase domain of osmosensor EnvZ. J roles of the periplasmic proteins. Proc Natl Acad Sci USA Bacteriol 1994;176:1157–63. 2014;111:15373–8. Behling LA, Hartsel SC, Lewis DE et al. NMR, mass spectrometry Cha JS, Cooksey DA. Copper hypersensitivity and uptake in and chemical evidence reveal a different chemical structure Pseudomonas syringae containing cloned components of the for methanobactin that contains oxazolone rings. JAmChem copper resistance operon. Appl Environ Microbiol 1993;59: Soc 2008;130:12604–5. 1671–4. Belabed BE, Meddour A, Samraoui B et al. Modeling seasonal Chalmers G, Rozas KM, Amachawadi RG et al. Distribution of the and spatial contamination of surface waters and upper sedi- pco gene cluster and associated genetic determinants among ments with trace metal elements across industrialized urban swine Escherichia coli from a controlled feeding trial. Genes areas of the Seybouse watershed in North Africa. Environ (Basel) 2018;9:504. Monit Assess 2017;189:265. Changela A, Chen K, Xue Y et al. Molecular basis of metal- Beolchini F, Pagnanelli F, Toro L et al. Ionic strength effect on ion selectivity and zeptomolar sensitivity by CueR. Science copper biosorption by Sphaerotilus natans: equilibrium study 2003;301:1383–7. and dynamic modelling in membrane reactor. Water Res Chaplin AK, Tan BG, Vijgenboom E et al. Copper trafficking in 2006;40:144–52. the CsoR regulon of Streptomyces lividans. Metallomics 2015;7: Bereza-Malcolm LT, Mann G, Franks AE. Environmental sensing 145–55. of heavy metals through whole cell microbial biosensors: a Chen XC, Wang YP, Lin Q et al. Biosorption of copper(II) and synthetic biology approach. ACS Synth Biol 2015;4:535–46. zinc(II) from aqueous solution by Pseudomonas putida CZ1. Billman-Jacobe H, Liu Y, Haites R et al. pSTM6-275, a conjuga- Colloids Surf B Biointerfaces 2005;46:101–7. tive IncHI2 plasmid of Salmonella enterica that confers antibi- Chillappagari S, Miethke M, Trip H et al. Copper acquisition is otic and heavy-metal resistance under changing physiologi- mediated by YcnJ and regulated by YcnK and CsoR in Bacillus cal conditions. Antimicrob Agents Chemother 2018;62. subtilis. J Bacteriol 2009;191:2362–70. Giachino et al. 9

Chi TD, Lee J-c, Pandey BD et al. Bioleaching of gold and copper Fang L, Li X, Li L et al. Co-spread of metal and antibiotic resis- from waste mobile phone PCBs by using a cyanogenic bac- tance within ST3-IncHI2 plasmids from E. coli isolates of terium. Miner Eng 2011;24:1219–22. food-producing animals. Sci Rep 2016;6:25312. Choi Y, Park TJ, Lee DC et al. Recombinant Escherichia coli as a bio- Faramarzi MA, Stagars M, Pensini E et al. Metal solubilization factory for various single- and multi-element nanomaterials. from metal-containing solid materials by cyanogenic Chro- Proc Natl Acad Sci USA 2018;115:5944–9. mobacterium violaceum. J Biotechnol 2004;113:321–6. Cobine P, Wickramasinghe WA, Harrison MD et al. The Entero- Feng S, Yang H, Wang W. Microbial community succession coccus hirae copper chaperone CopZ delivers copper(I) to the mechanism coupling with adaptive evolution of adsorption CopY repressor. FEBS Lett 1999;445:27–30. performance in chalcopyrite bioleaching. Bioresour Technol Cobine PA, George GN, Jones CE et al. Copper transfer from the 2015;191:37–44. Cu(I) chaperone, CopZ, to the repressor, Zn(II)CopY: metal Festa RA, Thiele DJ. Copper: an essential metal in biology. Curr coordination environments and protein interactions. Bio- Biol 2011;21:R877–R83.

chemistry 2002;41:5822–9. Fonti V, Dell’Anno A, Beolchini F. Does bioleaching represent a Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 Coppin JD, Villamaria FC, Williams MD et al. Self-sanitizing biotechnological strategy for remediation of contaminated copper-impregnated surfaces for bioburden reduction in sediments? Sci Total Environ 2016;563-564:302–19. patient rooms. Am J Infect Control 2017;45:692–4. Frangipani E, Haas D. Copper acquisition by the SenC protein Cornu J-Y, Huguenot D, Jez´ equel´ K et al. Bioremediation of regulates aerobic respiration in Pseudomonas aeruginosa PAO1. copper-contaminated soils by bacteria. World J Microbiol FEMS Microbiol Lett 2009;298:234–40. Biotechnol 2017;33:26. Franke S, Grass G, Nies DH. The product of the ybdE gene of the Das S, Dash HR, Chakraborty J. Genetic basis and importance of Escherichia coli chromosome is involved in detoxification of metal resistant genes in bacteria for bioremediation of con- silver ions. Microbiology 2001;147:965–72. taminated environments with toxic metal pollutants. Appl Funari V, Makinen¨ J, Salminen J et al. Metal removal from munic- Microbiol Biotechnol 2016;100:2967–84. ipal solid waste incineration fly ash: a comparison between Decaria L, Bertini I, Williams RJ. Copper proteomes, phylogenet- chemical leaching and bioleaching. Waste Manage (Oxford) ics and evolution. Metallomics 2011;3:56–60. 2017;60:397–406. De Paepe B, Peters G, Coussement P et al. Tailor-made transcrip- Fu Y, Bruce KE, Wu H et al. The S2 Cu(I) site in CupA from Strep- tional biosensors for optimizing microbial cell factories. JInd tococcus pneumoniae is required for cellular copper resistance. Microbiol Biotechnol 2017;44:623–45. Metallomics 2016;8:61–70. DiSpirito AA, Semrau JD, Murrell JC et al. Methanobactin and the Fu Y, Tsui H-CT, Bruce KE et al. A new structural paradigm in link between copper and bacterial methane oxidation. Micro- copper resistance in Streptococcus pneumoniae. Nat Chem Biol biol Mol Biol Rev 2016;80:387–409. 2013;9:177–83. Djoko KY, McEwan AG. Antimicrobial action of copper Is ampli- Gadd GM. Metals, minerals and microbes: geomicrobiology and fied via inhibition of heme biosynthesis. ACS Chem Biol bioremediation. Microbiology 2010;156:609–43. 2013;8:2217–23. Gale GAR, Schiavon Osorio AA, Mills LA et al. Emerging species Dollwet H, Sorenson JRJ. Historic uses of copper compounds in and genome editing tools: Future prospects in cyanobacterial medicine. Trace Elem Med 1985;2:80–7. synthetic biology. Microorganisms 2019;7:409. Drees SL, Beyer DF, Lenders-Lomscher C et al. Distinct functions Ghaed S, Shirazi EK, Marandi R. Biosorption of copper ions

of serial metal-binding domains in the Escherichia coli P1B- by Bacillus and Aspergillus species. Adsorp Sci Technol ATPase CopA. Mol Microbiol 2015;97:423–38. 2013;31:869–90. Drob´ıkova´ K, Rozumova´ L, Otoupal´ıkovaH´ et al. Bioleaching of Giachino A, Waldron KJ. Copper tolerance in bacteria requires hazardous waste. Chem Pap 2015;69:1193–201. the activation of multiple accessory pathways. Mol Microbiol Dunbar WS. Biotechnology and the mine of tomorrow. Trends 2020;114:377–90. Biotechnol 2017;35:79–89. Gillan DC, Van Camp C, Mergeay M et al. Paleomicrobiology EC Scientific Committees. Opinion on synthetic biology II: risk to investigate copper resistance in bacteria: isolation and assessment methodologies and safety aspects, European description of Cupriavidus necator B9 in the soil of a medieval Union, 2015. DOI: 10.2772/63529. foundry. Environ Microbiol 2017;19:770–87. Egler M, Grosse C, Grass G et al. Role of the extracytoplasmic Giner-Lamia J, Lopez-Maury´ L, Florencio FJ. CopM is a novel function protein family sigma factor RpoE in metal resis- copper-binding protein involved in copper resistance tance of Escherichia coli. J Bacteriol 2005;187:2297–307. in Synechocystis sp. PCC 6803. MicrobiologyOpen 2015;4: El-Bestawy E. Treatment of mixed domestic–industrial 167–85. wastewater using cyanobacteria. J Ind Microbiol Biotech- Giner-Lamia J, Lopez-Maury´ L, Reyes JC et al. The CopRS two- nol 2008;35:1503–16. component system is responsible for resistance to copper in El Ghazouani A, BasleA,GrayJ´ et al. Variations in methanobactin the cyanobacterium Synechocystis sp. PCC 6803. Plant Physiol structure influences copper utilization by methane- 2012;159:1806–18. oxidizing bacteria. Proc Natl Acad Sci U S A 2012;109:8400–4. Gold B, Deng H, Bryk R et al. Identification of a copper-binding European Parliament and Council. Directive 2001/18/EC of the metallothionein in pathogenic mycobacteria. Nat Chem Biol European Parliament and of the Council of 12 March 2001 2008;4:609–16. on the deliberate release into the environment of genet- Gomes HI, Funari V, Ferrari R. Bioleaching for resource recov- ically modified organisms and repealing Council Directive ery from low-grade wastes like fly and bottom ashes from 90/220/EEC. In: Council EPa (ed.), European Parliament and municipal incinerators: a SWOT analysis. Sci Total Environ Council, 2001. 2020;715:136945. Fang D, Zhang R, Zhou L et al. A combination of bioleaching and Gonzalez-Guerrero´ M, Raimunda D, Cheng X et al. Distinct func- bioprecipitation for deep removal of contaminating metals tional roles of homologous Cu+ efflux ATPases in Pseu- from dredged sediment. J Hazard Mater 2011;192:226–33. domonas aeruginosa. Mol Microbiol 2010;78:1246–58. 10 FEMS Microbiology Ecology, 2021, Vol. 97, No. 2

Grass G, Rensing C, Solioz M. Metallic copper as an antimicrobial Johnson MDL, Kehl-Fie TE, Klein R et al. Role of copper efflux in surface. Appl Environ Microbiol 2011;77:1541–7. pneumococcal pathogenesis and resistance to macrophage- Gudipaty SA, McEvoy MM. The histidine kinase CusS senses sil- mediated immune clearance. Infect Immun 2015;83:1684–94. ver ions through direct binding by its sensor domain. Biochim Kaksonen AH, Boxall NJ, Usher KM et al. Biosolubilisation of met- Biophys Acta 2014;1844:1656–61. als and metalloids. In: Rene ER, Sahinkaya E, Lewis A, Lens Gumulya Y, Boxall NJ, Khaleque HN et al. In a quest for engineer- PNL (eds.) Sustainable Heavy Metal Remediation: Volume 1: Prin- ing acidophiles for biomining applications: challenges and ciples and Processes. Cham: Springer International Publishing, opportunities. Genes 2018;9:116. 2017, 233–83. Guo Z, Zhang L, Cheng Y et al. Effects of pH, pulp density and Kaksonen AH, Lavonen L, Kuusenaho M et al. Bioleaching and particle size on solubilization of metals from a Pb/Zn smelt- recovery of metals from final slag waste of the copper smelt- ing slag using indigenous moderate thermophilic bacteria. ing industry. Miner Eng 2011;24:1113–21. Hydrometallurgy 2010;104:25–31. Kenney GE, Rosenzweig AC. Chalkophores. Annu Rev Biochem

Gupta P, Diwan B. Bacterial exopolysaccharide mediated heavy 2018;87:645–76. Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 metal removal: a review on biosynthesis, mechanism and Khalfaoui-Hassani B, Astier C, Nitschke W et al. CtpA, a remediation strategies. Biotechnol Rep 2017;13:58–71. copper-translocating P-type ATPase involved in the bio- Gomez-Santos´ N, Perez´ J, Sanchez-Sutil´ MC et al. CorE from genesis of multiple copper-requiring enzymes. J Biol Chem Myxococcus xanthus Is a copper-dependent RNA polymerase 2010;285:19330–7. sigma factor. PLos Genet 2011;7:e1002106. Khan AZ, Bilal M, Mehmood S et al. State-of-the-art genetic Haeili M, Moore C, Davis CJC et al. Copper complexation screen modalities to engineer cyanobacteria for sustainable biosyn- reveals compounds with potent antibiotic properties against thesis of biofuel and fine-chemicals to meet bio-economy methicillin-resistant Staphylococcus aureus. Antimicrob Agents challenges. Life (Basel, Switzerland) 2019;9:54. Chemother 2014;58:3727–36. Kimber RL, Lewis EA, Parmeggiani F et al. Biosynthesis and char- Han Y, Wang T, Chen G et al. A Pseudomonas aeruginosa type VI acterization of copper nanoparticles using Shewanella onei- secretion system regulated by CueR facilitates copper acqui- densis: application for click chemistry. Small 2018;14:1703145. sition. PLoS Pathog 2019;15:e1008198. Kimber RL, Parmeggiani F, Joshi N et al. Synthesis of cop- Hawari AH, Mulligan CN. Biosorption of lead(II), cadmium(II), per catalysts for click chemistry from distillery wastewater copper(II) and nickel(II) by anaerobic granular biomass. Biore- using magnetically recoverable bionanoparticles. Green Chem sour Technol 2006;97:692–700. 2019;21:4020–4. Hewett JP, Wolfe AK, Bergmann RA et al. Human health and envi- Kim HJ, Jeong H, Lee SJ. Synthetic biology for microbial heavy ronmental risks posed by synthetic biology R&D for energy metal biosensors. Anal Bioanal Chem 2018;410:1191–203. applications: a literature analysis. Appl Biosaf 2016;21:177–84. Kittleson JT, Loftin IR, Hausrath AC et al. Periplasmic metal- Hirooka K, Edahiro T, Kimura K et al. Direct and indirect regula- resistance protein CusF exhibits high affinity and specificity tion of the ycnKJI operon involved in copper uptake through for both CuI and AgI. Biochemistry 2006;45:11096–102. two transcriptional repressors, YcnK and CsoR, in Bacillus Klink C, Eisen S, Daus B et al. Investigation of Acidithiobacillus fer- subtilis. J Bacteriol 2012;194:5675–87. rooxidans in pure and mixed-species culture for bioleaching Huertas MJ, Lopez-Maury´ L, Giner-Lamia J et al. Metals in of Theisen sludge from former copper smelting. J Appl Micro- cyanobacteria: analysis of the copper, nickel, cobalt and biol 2016;120:1520–30. arsenic homeostasis mechanisms. Life 2014;4:865–86. Knapp CW, Fowle DA, Kulczycki E et al. Methane monooxyge- Huffman DL, Huyett J, Outten FW et al. Spectroscopy of Cu(II)- nase gene expression mediated by methanobactin in the PcoC and the multicopper oxidase function of PcoA, two presence of mineral copper sources. Proc Natl Acad Sci USA essential components of Escherichia coli pco copper resistance 2007;104:12040–5. operon. Biochemistry 2002;41:10046–55. Koh E-I, Robinson AE, Bandara N et al. Copper import in Ilyas S, Lee JC, Shin DY et al. Bio-hydrometallurgical processing Escherichia coli by the yersiniabactin metallophore system. of non-ferrous metals from copper smelting slag. Adv Mat Res Nat Chem Biol 2017;13:1016. 2013;825:250–3. Kremling K, Hydes D. Summer distribution of dissolved Al, Cd, Inkinen J, Makinen¨ R, Keinanen-Toivola¨ MM et al. Copper as an Co, Cu, Mn and Ni in surface waters around the British Isles. antibacterial material in different facilities. Lett Appl Microbiol Cont Shelf Res 1988;8:89–105. 2017;64:19–26. Kulczycki E, Fowle DA, Knapp C et al. Methanobactin-promoted Ishigaki T, Nakanishi A, Tateda M et al. Bioleaching of metal from dissolution of Cu-substituted borosilicate glass. Geobiology municipal waste incineration fly ash using a mixed culture 2007;5:251–63. of sulfur-oxidizing and iron-oxidizing bacteria. Chemosphere Kwon M, Ho A, Yoon S. Novel approaches and reasons to iso- 2005;60:1087–94. late methanotrophic bacteria with biotechnological poten- Jaejoon J, Sang Jun L. Biochemical and biodiversity insights into tials: recent achievements and perspectives. Appl Microbiol heavy metal ion-responsive transcription regulators for syn- Biotechnol 2019;103:1–8. thetic biological heavy metal sensors. J Microbiol Biotechnol Lacerda ECM, dos Passos Galluzzi Baltazar M, dos Reis TA 2019;29:1522–42. et al. Copper biosorption from an aqueous solution by the Jimenez-D´ ´ıaz L, Caballero A, Perez-Hern´ andez´ N et al. Microbial dead biomass of Penicillium ochrochloron. Environ Monit Assess alkane production for jet fuel industry: motivation, state of 2019;191:247. the art and perspectives. Microb Biotechnol 2017;10:103–24. Ladomersky E, Khan A, Shanbhag V et al. Host and pathogen Johnson DB. Development and application of biotechnologies copper-transporting P-Type ATPases function antag- in the metal mining industry. Environ Sci Pollut Res 2013;20: onistically during Salmonella infection. Infect Immun 7768–76. 2017;85:e00351–17. Giachino et al. 11

Lalitha K, Kalaimurgan D, Nithya K et al. Antibacterial, antifungal Meulepas RJW, Gonzalez-Gil G, Teshager FM et al. Anaerobic and mosquitocidal efficacy of copper nanoparticles synthe- bioleaching of metals from waste activated sludge. Sci Total sized from entomopathogenic nematode: Insect–host rela- Environ 2015;514:60–7. tionship of bacteria in secondary metabolites of Morganella Michels HT, Keevil CW, Salgado CD et al. From laboratory morganii sp. (PMA1). Arab J Sci Eng 2020;45:4489–501. research to a clinical trial: copper alloy surfaces kill bacteria Lamichhane JR, Osdaghi E, Behlau F et al. Thirteen decades of and reduce hospital-acquired infections. Herd 2015;9:64–79. antimicrobial copper compounds applied in agriculture. A Miller AR, Densmore CD, Degens ET et al. Hot brines and recent review. Agron Sustain Dev 2018;38:28. iron deposits in deeps of the Red Sea. Geochim Cosmochim Acta Latorre M, Cortes´ MP, Travisany D et al. The bioleaching potential 1966;30:341–59. of a bacterial consortium. Bioresour Technol 2016;218:659–66. Modin O, Aulenta F. Three promising applications of microbial Lawton TJ, Kenney GE, Hurley JD et al. The CopC fam- electrochemistry for the water sector. Environ Sci Water Res ily: structural and bioinformatic insights into a diverse Technol 2017;3:391–402.

group of periplasmic copper binding proteins. Biochemistry Mohapatra H, Gupta R. Concurrent sorption of Zn(II), Cu(II) Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 2016;55:2278–90. and Co(II) by Oscillatoria angustissima asafunctionofpHin Lee J, Dennison C. Cytosolic copper binding by a bacterial stor- binary and ternary metal solutions. Bioresour Technol 2005;96: age protein and interplay with copper efflux. Int J Mol Sci 1387–98. 2019;20:4144. Morosov X, Davoudi C-F, Baumgart M et al. The copper- Lee SM, Grass G, Rensing C et al. The Pco proteins are involved deprivation stimulon of Corynebacterium glutamicum in periplasmic copper handling in Escherichia coli. Biochem Bio- comprises proteins for biogenesis of the actinobac-

phys Res Comm 2002;295:616–20. terial cytochrome bc1–aa3 supercomplex. J Biol Chem Li F, Lei C, Shen Q et al. Analysis of copper nanoparticles toxi- 2018;293:15628–40. city based on a stress-responsive bacterial biosensor array. Nagorski SA, McKinnon TE, Moore JN. Seasonal and storm-scale Nanoscale 2013a;5:653–62. variations in heavy metal concentrations of two mining- Li M, Cheng X, Guo H. Heavy metal removal by biomineralization contaminated streams, Montana, U.S.A. J Phys IV France of urease producing bacteria isolated from soil. Int Biodeterior 2003;107:909–. Biodegradation 2013b;76:81–5. Nakajima A, Yasuda M, Yokoyama H et al. Copper biosorption by Li P-S, Peng Z-W, Su J et al. Construction and optimization of chemically treated Micrococcus luteus cells. World J Microbiol a Pseudomonas putida whole-cell bioreporter for detection of Biotechnol 2001;17:343–7. bioavailable copper. Biotechnol Lett 2014;36:761–6. Nancharaiah YV, Venkata Mohan S, Lens PNL. Metals removal Liu J, He X-x, Lin X-r et al. Ecological effects of combined pol- and recovery in bioelectrochemical systems: a review. Biore- lution associated with e-waste recycling on the composition sour Technol 2015;195:102–14. and diversity of soil microbial communities. Environ Sci Tech- Nicholson FA, Smith SR, Alloway BJ et al. Aninventoryofheavy nol 2015;49:6438–47. metals inputs to agricultural soils in England and Wales. Sci Li X, Islam MM, Chen L et al. Metagenomics-guided discovery Total Environ 2003;311:205–19. of potential bacterial metallothionein genes from the soil Ni H, Xiong Z, Ye T et al. Biosorption of copper(II) from aque- microbiome that confer Cu and/or Cd resistance. Appl Env- ous solutions using volcanic rock matrix-immobilized Pseu- iron Microbiol 2020;86:e02907–19. domonas putida cells with surface-displayed cyanobacterial Lu W-B, Shi J-J, Wang C-H et al. Biosorption of lead, copper and metallothioneins. Chem Eng J 2012;204-206:264–71. cadmium by an indigenous isolate Enterobacter sp. J1 pos- Novoa-Aponte L, Ram´ırez D, Arguello¨ JM. The interplay of the sessing high heavy-metal resistance. J Hazard Mater 2006;134: metallosensor CueR with two distinct CopZ chaperones 80–6. defines copper homeostasis in Pseudomonas aeruginosa. J Biol Macomber L, Imlay JA. The iron-sulfur clusters of dehydratases Chem 2019;294:4934–45. are primary intracellular targets of copper toxicity. Proc Natl O’Brien H, Alvin JW, Menghani SV et al. Rules of expansion: an Acad Sci USA 2009;106:8344–9. updated consensus operator site for the CopR-CopY fam- Martinez AR, Heil JR, Charles TC. An engineered GFP fluorescent ily of bacterial copper exporter system repressors. mSphere bacterial biosensor for detecting and quantifying silver and 2020;5:e00411–20. copper ions. Biometals 2019;32:265–72. Orell A, Navarro CA, Arancibia R et al. Life in blue: copper resis- McNerney MP, Watstein DM, Styczynski MP. Precision metabolic tance mechanisms of Bacteria and Archaea used in indus- engineering: the design of responsive, selective, and control- trial biomining of minerals. Biotechnol Adv 2010;28:839–48. lable metabolic systems. Metab Eng 2015;31:123–31. Osman D, Patterson C, Bailey K et al. The copper supply pathway Mealman TD, Bagai I, Singh P et al. Interactions between CusF to a Salmonella Cu,Zn-superoxide dismutase (SodCII) involves and CusB identified by NMR spectroscopy and chemical P1B-type ATPase copper efflux and periplasmic CueP. Mol cross-linking coupled to mass spectrometry. Biochemistry Microbiol 2012;87:466–77. 2011;50:2559–66. Osman D, Waldron KJ, Denton H et al. Copper homeostasis in Meer I, Nazir R. Removal techniques for heavy metals from fly Salmonella is atypical and copper-CueP is a major periplasmic ash. J Mater Cycles Waste Manage 2018;20:703–22. metal complex. J Biol Chem 2010;285:25259–68. Mejias Carpio IE, Machado-Santelli G, Kazumi Sakata S et al. Outten FW, Huffman DL, Hale JA et al. The independent Copper removal using a heavy-metal resistant microbial cue and cus systems confer copper tolerance during aer- consortium in a fixed-bed reactor. Water Res 2014;62: obic and anaerobic growth in Escherichia coli. J Biol Chem 156–66. 2001;276:30670–7. Mermod M, Magnani D, Solioz M et al. The copper-inducible Oves M, Khan MS, Zaidi A. Biosorption of heavy metals by ComR (YcfQ) repressor regulates expression of ComC (YcfR), Bacillus thuringiensis strain OSM29 originating from indus- which affects copper permeability of the outer membrane of trial effluent contaminated north Indian soil. Saudi J Biol Sci Escherichia coli. Biometals 2012;25:33–43. 2013;20:121–9. 12 FEMS Microbiology Ecology, 2021, Vol. 97, No. 2

Ozt¨ urk¨ A, Artan T, Ayar A. Biosorption of nickel(II) and copper(II) Purac´ J, Nikolic´ TV, KojicD´ et al. Identification of a metal- ions from aqueous solution by Streptomyces coelicolor A3(2). lothionein gene in honey bee Apis mellifera and its expres- Colloids Surf B Biointerfaces 2004;34:105–11. sion profile in response to Cd, Cu and Pb exposure. Mol Ecol Padilla-Benavides T, George Thompson AM, McEvoy MM 2019;28:731–45. et al. Mechanism of ATPase-mediated Cu+ export and Purves J, Thomas J, Riboldi GP et al. A horizontally gene trans- delivery to periplasmic chaperones: the interaction of ferred copper resistance locus confers hyper-resistance to Escherichia coli CopA and CusF. J Biol Chem 2014;289: antibacterial copper toxicity and enables survival of com- 20492–501. munity acquired methicillin resistant Staphylococcus aureus Palanivel TM, Sivakumar N, Al-Ansari A et al. Bioremediation USA300 in macrophages. Environ Microbiol 2018;20:1576–89. of copper by active cells of Pseudomonas stutzeri LA3 iso- Perez´ J, Munoz-Dorado˜ J, Moraleda-Munoz˜ A. The complex global lated from an abandoned copper mine soil. J Environ Manage response to copper in the multicellular bacterium Myxococcus 2020;253:109706. xanthus. Metallomics 2018;10:876–86.

Pantidos N, Edmundson MC, Horsfall L. Room temperature bio- Qin Y, Hasman H, Aarestrup FM et al. Genome sequences of three Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 production, isolation and anti-microbial properties of sta- highly copper-resistant Salmonella enterica subsp. I serovar ble elemental copper nanoparticles. N Biotechnol 2018;40: Typhimurium strains Isolated from pigs in Denmark. Genome 275–81. Announc 2014;2:e01334–14. Pardo R, Herguedas M, Barrado E et al. Biosorption of cadmium, Rademacher C, Masepohl B. Copper-responsive gene regulation copper, lead and zinc by inactive biomass of Pseudomonas in bacteria. Microbiology 2012;158:2451–64. putida. Anal Bioanal Chem 2003;376:26–32. Raff J, Soltmann U, Matys S et al. Biosorption of uranium and Peariso K, Huffman DL, Penner-Hahn JE et al. The PcoC copper copper by biocers. Chem Mater 2003;15:240–4. resistance protein coordinates Cu(I) via novel S-methionine Raimunda D, Gonzalez-Guerrero´ M, Leeber BW et al. The trans- + interactions. JAmChemSoc2003;125:342–3. port mechanism of bacterial Cu -ATPases: distinct efflux Pesch M-L, Hoffmann M, Christl I et al. Competitive lig- rates adapted to different function. Biometals 2011;24:467–75. and exchange between Cu–humic acid complexes and Raimunda D, Padilla-Benavides T, Vogt S et al. Periplasmic methanobactin. Geobiology 2013;11:44–54. response upon disruption of transmembrane Cu transport in Philips SJ, Canalizo-Hernandez M, Yildirim I et al. Allosteric tran- Pseudomonas aeruginosa. Metallomics 2013;5:144–51. scriptional regulation via changes in the overall topology of Ramanathan R, Field MR, O’Mullane AP et al. Aqueous phase syn- thecorepromoter.Science 2015;349:877–81. thesis of copper nanoparticles: a link between heavy metal Planet PJ, Diaz L, Kolokotronis SO et al. Parallel epidemics resistance and nanoparticle synthesis ability in bacterial sys- of community-associated methicillin-resistant Staphylococ- tems. Nanoscale 2013;5:2300–6. cus aureus USA300 infection in North and South America. J Rao M, Liu H, Yang M et al. A copper-responsive global repressor Infect Dis 2015;212:1874–82. regulates expression of diverse membrane-associated trans- Pollmann K, Kutschke S, Matys S et al. Bio-recycling of metals: porters and bacterial drug resistance in mycobacteria. J Biol recycling of technical products using biological applications. Chem 2012;287:39721–31. Biotechnol Adv 2018;36:1048–62. Ravikumar S, Baylon MG, Park SJ et al. Engineered microbial Pontel LB, Soncini FC. Alternative periplasmic copper-resistance biosensors based on bacterial two-component systems as mechanisms in Gram negative bacteria. Mol Microbiol synthetic biotechnology platforms in bioremediation and 2009;73:212–25. biorefinery. Microb Cell Fact 2017;16:62. Posacka AM, Semeniuk DM, Whitby H et al. Dissolved cop- Ravikumar S, Ganesh I, Yoo I-k et al. Construction of a bac- per (dCu) biogeochemical cycling in the subarctic Northeast terial biosensor for zinc and copper and its application to Pacific and a call for improving methodologies. Mar Chem the development of multifunctional heavy metal adsorption 2017;196:47–61. bacteria. Process Biochem 2012;47:758–65. Potysz A, Grybos M, Kierczak J et al. Bacterially-mediated weath- Ravikumar S, I-k Y, Lee SY et al. Construction of copper remov- ering of crystalline and amorphous Cu-slags. Appl Geochem ing bacteria through the integration of two-component 2016a;64:92–106. system and cell surface display. Appl Biochem Biotechnol Potysz A, Kierczak J. Prospective (bio)leaching of historical 2011;165:1674–81. copper slags as an alternative to their disposal. Minerals Rawlings DE. Heavy metal mining using microbes. Annu Rev 2019;9:542. Microbiol 2002;56:65–91. Potysz A, Lens PNL, van de Vossenberg J et al. Compari- Rehman M, Liu L, Wang Q et al. Copper environmental toxicol- son of Cu, Zn and Fe bioleaching from Cu-metallurgical ogy, recent advances, and future outlook: a review. Environ slags in the presence of Pseudomonas fluorescens and Sci Pollut Res 2019;26:18003–16. Acidithiobacillus thiooxidans. Appl Geochem 2016b;68: Rensing C, Grass G. Escherichia coli mechanisms of copper 39–52. homeostasis in a changing environment. FEMS Microbiol Rev Potysz A, van Hullebusch ED, Kierczak J et al. Copper metallur- 2003;27:197–213. gical slags – Current knowledge and fate: a review. Crit Rev Ressler T, Kniep BL, Kasatkin I et al. The microstructure of copper Environ Sci Technol 2015;45:2424–88. zinc oxide catalysts: bridging the materials gap. Angew Chem Poulsen HD. Zinc and copper as feed additives, growth factors Int Ed 2005;44:4704–7. or unwanted environmental factors. J Anim Feed Sci 1998;7: Robinson NJ, Winge DR. Copper metallochaperones. Annu Rev 135–42. Biochem 2010;79:537–62. Pourhossein F, Mousavi SM. Enhancement of copper, nickel, Rosario-Cruz Z, Eletsky A, Daigham NS et al. The copBL operon and gallium recovery from LED waste by adaptation protects Staphylococcus aureus from copper toxicity: CopL is of Acidithiobacillus ferrooxidans. Waste Manage (Oxford) an extracellular membrane-associated copper-binding pro- 2018;79:98–108. tein. J Biol Chem 2019;294:4027–44. Giachino et al. 13

Ross MO, MacMillan F, Wang J et al. Particulate methane Tarrant E, G PR, McIlvin MR et al. Copper stress in Staphylo- monooxygenase contains only mononuclear copper centers. coccus aureus leads to adaptive changes in central carbon Science 2019;364:566–70. metabolism. Metallomics 2019;11:183–200. Ro SY, Rosenzweig AC. Recent advances in the genetic manip- Thakur P, Kumar S. Metallurgical processes unveil the unex- ulation of Methylosinus trichosporium OB3b. Methods Enzymol plored “sleeping mines” e- waste: a review. Environ Sci Pollut 2018;605:335–49. Res 2020;27:32359–70. Rouch DA, Brown NL. Copper-inducible transcriptional regula- Thompson AK, Smith D, Gray J et al. Mutagenic analysis of Cox11

tion at two promoters in the Escherichia coli copper resistance of Rhodobacter sphaeroides: Insights into the assembly of CuB determinant pco. Microbiology 1997;143:1191–202. of cytochrome c oxidase. Biochemistry 2010;49:5651–61. Ruparelia JP, Chatterjee AK, Duttagupta SP et al. Strain specificity Tottey S, Patterson CJ, Banci L et al. Cyanobacterial metallochap- in antimicrobial activity of silver and copper nanoparticles. erone inhibits deleterious side reactions of copper. Proc Natl Acta Biomater 2008;4:707–16. Acad Sci U S A 2012;109:95–100.

Sakamoto K, Agari Y, Agari K et al. Structural and functional Tountas AA, Peng X, Tavasoli AV et al. Towards solar methanol: Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 characterization of the transcriptional repressor CsoR from past, present, and future. Adv Sci 2019;6:1801903. Thermus thermophilus HB8. Microbiology 2010;156:1993–2005. Tunali S, C¸ abuk A, Akar T. Removal of lead and copper ions from Schippers A. Microorganisms involved in bioleaching and aqueous solutions by bacterial strain isolated from soil. Chem nucleic acid-based molecular methods for their identifica- Eng J 2006;115:203–11. tion and quantification. In: Donati ER, Sand W (eds.) Microbial U.S. Geological Survey. Mineral commodity summaries 2020. Processing of Metal Sulfides. Dordrecht: Springer Netherlands, Reston, VA, 2020, DOI: 10.3133/mcs2020. 2007, 3–33. Udagedara SR, Wijekoon CJK, Xiao Z et al. The crystal struc- Sethurajan M, van Hullebusch ED, Nancharaiah YV. Biotech- ture of the CopC protein from Pseudomonas fluorescens reveals nology in the management and resource recovery from amended classifications for the CopC protein family. JInorg metal bearing solid wastes: recent advances. J Environ Man- Biochem 2019;195:194–200. age 2018;211:138–53. Ueki T, Sakamoto Y, Yamaguchi N et al. Bioaccumulation of cop- Sharma S, Rosato A. Role of the N-terminal tail of metal- per ions by Escherichia coli expressing vanabin genes from the

transporting P1B-type ATPases from genome-wide analy- vanadium-rich ascidian Ascidia sydneiensis samea. Appl Envi- sis and molecular dynamics simulations. J Chem Inf Model ron Microbiol 2003;69:6442–6. 2009;49:76–83. UK Parliament. Genetically modified organisms (Deliberate Simon AJ, Ellington AD. Recent advances in synthetic biosafety. Release) regulations 2002; Statutory instrument 2002 No. F1000Research 2016;5(F1000 Faculty Rev):2118. 2443, 2002. Singh P, Purakayastha TJ, Mitra S et al. River water irrigation with United Nations General Assembly. Transforming our world: The heavy metal load influences soil biological activities and risk 2030 agenda for sustainable development: United Nations, factors. J Environ Manage 2020;270:110517. 2015. Singh V. Recent advances and opportunities in synthetic logic Urbina J, Patil A, Fujishima K et al. A new approach to biomin- gates engineering in living cells. Syst Synth Biol 2014;8: ing: bioengineering surfaces for metal recovery from aque- 271–82. ous solutions. Sci Rep 2019;9:16422. Srichandan H, Mohapatra RK, Parhi PK et al. Bioleaching Uslu G, Tanyol M. Equilibrium and thermodynamic parameters approach for extraction of metal values from secondary solid of single and binary mixture biosorption of lead (II) and cop- wastes: a critical review. Hydrometallurgy 2019;189:105122. per (II) ions onto Pseudomonas putida: effect of temperature. J Stewart LJ, Thaqi D, Kobe B et al. Handling of nutrient copper in Hazard Mater 2006;135:87–93. the bacterial envelope. Metallomics 2019;11:50–63. Valdes´ J, Pedroso I, Quatrini R et al. Acidithiobacillus ferrooxidans Straw ML, Chaplin AK, Hough MA et al. A cytosolic copper stor- metabolism: from genome sequence to industrial applica- age protein provides a second level of copper tolerance in tions. BMC Genomics 2008;9:597. Streptomyces lividans. Metallomics 2018;10:180–93. Veneu DM, Torem ML, Pino GAH. Fundamental aspects of cop- Strong PJ, Xie S, Clarke WP. Methane as a resource: can per and zinc removal from aqueous solutions using a Strep- the methanotrophs add value? Environ Sci Technol 2015;49: tomyces lunalinharesii strain. Miner Eng 2013;48:44–50. 4001–18. Vestola EA, Kuusenaho MK, Narhi¨ HM et al. Acid bioleaching of Subedi P, Paxman JJ, Wang G et al. The Scs disulfide reduc- solid waste materials from copper, steel and recycling indus- tase system cooperates with the metallochaperone CueP in tries. Hydrometallurgy 2010;103:74–9. Salmonella copper resistance. J Biol Chem 2019;294:15876–88. Villafane AA, Voskoboynik Y, Cuebas M et al. Response to excess Suvorova IA, Korostelev YD, Gelfand MS. GntR family of copper in the hyperthermophile Sulfolobus solfataricus strain bacterial transcription factors and their DNA binding 98/2. Biochem Biophys Res Comm 2009;385:67–71. motifs: structure, positioning and co-evolution. PLoS One Vincent M, Hartemann P, Engels-Deutsch M. Antimicrobial 2015;10:e0132618. applications of copper. Int J Hyg Environ Health 2016;219: Swem DL, Swem LR, Setterdahl A et al. Involvement of SenC in 585–91. assembly of cytochrome c oxidase in Rhodobacter capsulatus. Vita N, Landolfi G, BasleA´ et al. Bacterial cytosolic proteins with J Bacteriol 2005;187:8081–7. a high capacity for Cu(I) that protect against copper toxicity. Sanchez-Sutil´ MC, Marcos-Torres FJ, Perez´ J et al. Dissection Sci Rep 2016;6:39065. of the sensor domain of the copper-responsive histidine Vita N, Platsaki S, BasleA´ et al. A four-helix bundle stores copper kinase CorS from Myxococcus xanthus. Environ Microbiol Rep for methane oxidation. Nature 2015;525:140–3. 2016;8:363–70. Volesky B. Biosorption and me. Water Res 2007;41:4017–29. Tapscott T, Guarnieri MT, Henard CA. Development of a von Rozycki T, Nies DH. Cupriavidus metallidurans:evolution CRISPR/Cas9 system for Methylococcus capsulatus in vivo gene of a metal-resistant bacterium. Antonie Van Leeuwenhoek editing. Appl Environ Microbiol 2019;85:e00340–19. 2009;96:115–39. 14 FEMS Microbiology Ecology, 2021, Vol. 97, No. 2

Vukojevic´ S, Trapp O, Grunwaldt J-D et al. Quasi-homogeneous Wijekoon CJK, Young TR, Wedd AG et al. CopC protein from Pseu- methanol synthesis over highly active copper nanoparticles. domonas fluorescens SBW25 features a conserved novel high- Angew Chem Int Ed 2005;44:7978–81. affinity Cu(II) binding site. Inorg Chem 2015;54:2950–9. Vullo DL, Ceretti HM, Daniel MA et al. Cadmium, zinc and cop- Williams RJP. A system’s view of the evolution of life. J R Soc Inter- per biosorption mediated by Pseudomonas veronii 2E. Bioresour face 2007;4:1049–70. Technol 2008;99:5574–81. Wilson B, Pyatt FB. Heavy metal dispersion, persistance, and Waldron KJ, Firbank SJ, Dainty SJ et al. Structure and metal bioccumulation around an ancient copper mine situated in loading of a soluble periplasm cuproprotein. J Biol Chem Anglesey, UK. Ecotoxicol Environ Saf 2007;66:224–31. 2010;285:32504–11. Wolschendorf F, Ackart D, Shrestha TB et al. Copper resistance is Wang B, Barahona M, Buck M. A modular cell-based biosen- essential for virulence of Mycobacterium tuberculosis. Proc Natl sor using engineered genetic logic circuits to detect and Acad Sci USA 2011;108:1621–6. integrate multiple environmental signals. Biosens Bioelectron Wong CSC, Wu SC, Duzgoren-Aydin NS et al. Trace metal con-

2013;40:368–76. tamination of sediments in an e-waste processing village in Downloaded from https://academic.oup.com/femsec/article/97/2/fiaa249/6021318 by guest on 30 September 2021 Wang F, Zhang W. Synthetic biology: recent progress, biosafety China. Environ Pollut 2007;145:434–42. and biosecurity concerns, and possible solutions. J Biosaf Xia M-C, Wang Y-P, Peng T-J et al. Recycling of metals from Biosecur 2019;1:22–30. pretreated waste printed circuit boards effectively in stirred WangJ,BaiJ,XuJet al. Bioleaching of metals from printed tank reactor by a moderately thermophilic culture. J Biosci wire boards by Acidithiobacillus ferrooxidans and Acidithiobacil- Bioeng 2017;123:714–21. + lus thiooxidans and their mixture. J Hazard Mater 2009;172: Yang J, Wu J, Feng P et al. Conversion of Cu2 -polluted biomass + 1100–5. into Cu2 -based metal-organic frameworks antibacterial Wang S, Zheng Y, Yan W et al. Enhanced bioleaching efficiency material to achieve recycling of pollutants. J Clean Prod of metals from e-wastes driven by biochar. J Hazard Mater 2020;261:121235. 2016;320:393–400. Zapotoczna M, Riboldi GP, Moustafa AM et al. Mobile-genetic- Warnes SL, Keevil CW. Lack of involvement of Fenton chemistry element-encoded hypertolerance to copper protects Staphy- in death of methicillin-resistant and methicillin-sensitive lococcus aureus from killing by host phagocytes. mBio strains of Staphylococcus aureus and destruction of their 2018;9:e00550–18. genomes on wet or dry copper alloy surfaces. Appl Environ Zeng Z, Zheng P, Kang D et al. The removal of copper Microbiol 2016;82:2132–6. and zinc from swine wastewater by anaerobic biological- Wendlandt K-D, Stottmeister U, Helm J et al. The potential of chemical process: performance and mechanism. J Hazard methane-oxidizing bacteria for applications in environmen- Mater 2021;401:123767. tal biotechnology. Eng Life Sci 2010;10:87–102. Zepeda VJ, Nancucheo I, Guillen M et al. Biological production Wernimont AK, Huffman DL, Finney LA et al. Crystal structure of copper sulfide concentrate from flotation tailings and low and dimerization equilibria of PcoC, a methionine-rich cop- grade ore. Solid State Phenomena 2017;262:202–6. per resistance protein from Escherichia coli. J Biol Inorg Chem Zhang F, Keasling J. Biosensors and their applications in micro- 2003;8:185–94. bial metabolic engineering. Trends Microbiol 2011;19:323–9. Whiddon KT, Gudneppanavar R, Hammer TJ et al. Fluorescence- Zhang L, Koay M, Maher MJ et al. Intermolecular transfer of cop- based analysis of the intracytoplasmic membranes per ions from the CopC protein of Pseudomonas syringae.Crys- of type I methanotrophs. Microb Biotechnol 2019;12: tal structures of fully loaded CuICuII forms. JAmChemSoc 1024–33. 2006;128:5834–50. White C, Lee J, Kambe T et al. A role for the ATP7A copper- Zhou T, Li R, Zhang S et al. A copper-specific microbial fuel transporting ATPase in macrophage bactericidal activity. J cell biosensor based on riboflavin biosynthesis of engineered Biol Chem 2009;284:33949–56. Escherichia coli. Biotechnol Bioeng 2020; ( In press). https://doi. WHO. Copper in drinking-water: background document for org/10.1002/bit.27563. development of WHO guidelines for drinking-water quality. Zhu N, Xiang Y, Zhang T et al. Bioleaching of metal concen- Geneva: World Health Organization, 2004. trates of waste printed circuit boards by mixed culture of aci- WHO. Guidelines for drinking-water quality,2nded,Vol. 1: Recom- dophilic bacteria. J Hazard Mater 2011;192:614–9. mendations. Geneva: World Health Organization, 1993, 46. Zimmermann M, Udagedara SR, Sze CM et al. PcoE — A metal Wightwick AM, Mollah MR, Partington DL et al. Copper fungi- sponge expressed to the periplasm of copper resistance cide residues in Australian vineyard soils. J Agric Food Chem Escherichia coli. Implication of its function role in copper resis- 2008;56:2457–64. tance. J Inorg Biochem 2012;115:186–97.