Escherichia coli in Auto(trophic) Mode.

It is challenging to convert a heterotrophic organism that loves sugars and other multicarbon compounds as energy and carbon sources into an autotroph that builds all biomass from carbon dioxide. In this issue, Gleizer et al. demonstrate how this can be achieved.

Room-temperature quantum optomechanics using an ultralow noise cavity.

At room temperature, mechanical motion driven by the quantum backaction of light has been observed only in pioneering experiments in which an optical restoring force controls the oscillator stiffness1,2. For solid-state mechanical resonators in which oscillations are controlled by the material rigidity, the observation of these effects has been hindered by low mechanical quality factors, optical cavity frequency fluctuations3, thermal intermodulation noise4,5 and photothermal instabilities. Here we overcome these challenges with a phononic-engineered membrane-in-the-middle system. By using phononic-crystal-patterned cavity mirrors, we reduce the cavity frequency noise by more than 700-fold. In this ultralow noise cavity, we insert a membrane resonator with high thermal conductance and a quality factor (Q) of 180 million, engineered using recently developed soft-clamping techniques6,7. These advances enable the operation of the system within a factor of 2.5 of the Heisenberg limit for displacement sensing8, leading to the squeezing of the probe laser by 1.09(1) dB below the vacuum fluctuations. Moreover, the long thermal decoherence time of the membrane oscillator (30 vibrational periods) enables us to prepare conditional displaced thermal states of motion with an occupation of 0.97(2) phonons using a multimode Kalman filter. Our work extends the quantum control of solid-state macroscopic oscillators to room temperature.

Lithium tantalate photonic integrated circuits for volume manufacturing.

Electro-optical photonic integrated circuits (PICs) based on lithium niobate (LiNbO3) have demonstrated the vast capabilities of materials with a high Pockels coefficient1,2. They enable linear and high-speed modulators operating at complementary metal-oxide-semiconductor voltage levels3 to be used in applications including data-centre communications4, high-performance computing and photonic accelerators for AI5. However, industrial use of this technology is hindered by the high cost per wafer and the limited wafer size. The high cost results from the lack of existing high-volume applications in other domains of the sort that accelerated the adoption of silicon-on-insulator (SOI) photonics, which was driven by vast investment in microelectronics. Here we report low-loss PICs made of lithium tantalate (LiTaO3), a material that has already been adopted commercially for 5G radiofrequency filters6 and therefore enables scalable manufacturing at low cost, and it has equal, and in some cases superior, properties to LiNbO3. We show that LiTaO3 can be etched to create low-loss (5.6 dB m-1) PICs using a deep ultraviolet (DUV) stepper-based manufacturing process7. We demonstrate a LiTaO3 Mach-Zehnder modulator (MZM) with a half-wave voltage-length product of 1.9 V cm and an electro-optic bandwidth of up to 40 GHz. In comparison with LiNbO3, LiTaO3 exhibits a much lower birefringence, enabling high-density circuits and broadband operation over all telecommunication bands. Moreover, the platform supports the generation of soliton microcombs. Our work paves the way for the scalable manufacture of low-cost and large-volume next-generation electro-optical PICs.

Emergence of fractal geometries in the evolution of a metabolic enzyme.

Fractals are patterns that are self-similar across multiple length-scales1. Macroscopic fractals are common in nature2-4; however, so far, molecular assembly into fractals is restricted to synthetic systems5-12. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpinski triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution.

A recently quenched galaxy 700 million years after the Big Bang.

Local and low-redshift (z < 3) galaxies are known to broadly follow a bimodal distribution: actively star-forming galaxies with relatively stable star-formation rates and passive systems. These two populations are connected by galaxies in relatively slow transition. By contrast, theory predicts that star formation was stochastic at early cosmic times and in low-mass systems1-4. These galaxies transitioned rapidly between starburst episodes and phases of suppressed star formation, potentially even causing temporary quiescence-so-called mini-quenching events5,6. However, the regime of star-formation burstiness is observationally highly unconstrained. Directly observing mini-quenched galaxies in the primordial Universe is therefore of utmost importance to constrain models of galaxy formation and transformation7,8. Early quenched galaxies have been identified out to redshift z < 5 (refs. 9-12) and these are all found to be massive (M⋆ > 1010 M⊙) and relatively old. Here we report a (mini-)quenched galaxy at z = 7.3, when the Universe was only 700 Myr old. The JWST/NIRSpec spectrum is very blue (U-V = 0.16 ± 0.03 mag) but exhibits a Balmer break and no nebular emission lines. The galaxy experienced a short starburst followed by rapid quenching; its stellar mass (4-6 × 108 M⊙) falls in a range that is sensitive to various feedback mechanisms, which can result in perhaps only temporary quenching.

A small and vigorous black hole in the early Universe.

Several theories have been proposed to describe the formation of black hole seeds in the early Universe and to explain the emergence of very massive black holes observed in the first thousand million years after the Big Bang1-3. Models consider different seeding and accretion scenarios4-7, which require the detection and characterization of black holes in the first few hundred million years after the Big Bang to be validated. Here we present an extensive analysis of the JWST-NIRSpec spectrum of GN-z11, an exceptionally luminous galaxy at z = 10.6, revealing the detection of the [NeIV]λ2423 and CII*λ1335 transitions (typical of active galactic nuclei), as well as semi-forbidden nebular lines tracing gas densities higher than 109 cm-3, typical of the broad line region of active galactic nuclei. These spectral features indicate that GN-z11 hosts an accreting black hole. The spectrum also reveals a deep and blueshifted CIVλ1549 absorption trough, tracing an outflow with velocity 800-1,000 km s-1, probably driven by the active galactic nucleus. Assuming local virial relations, we derive a black hole mass of log ( M BH / M ⊙ ) = 6.2 ± 0.3 , accreting at about five times the Eddington rate. These properties are consistent with both heavy seeds scenarios and scenarios considering intermediate and light seeds experiencing episodic super-Eddington phases. Our finding explains the high luminosity of GN-z11 and can also provide an explanation for its exceptionally high nitrogen abundance.

Ultrafast tunable lasers using lithium niobate integrated photonics.

Early works1 and recent advances in thin-film lithium niobate (LiNbO3) on insulator have enabled low-loss photonic integrated circuits2,3, modulators with improved half-wave voltage4,5, electro-optic frequency combs6 and on-chip electro-optic devices, with applications ranging from microwave photonics to microwave-to-optical quantum interfaces7. Although recent advances have demonstrated tunable integrated lasers based on LiNbO3 (refs. 8,9), the full potential of this platform to demonstrate frequency-agile, narrow-linewidth integrated lasers has not been achieved. Here we report such a laser with a fast tuning rate based on a hybrid silicon nitride (Si3N4)-LiNbO3 photonic platform and demonstrate its use for coherent laser ranging. Our platform is based on heterogeneous integration of ultralow-loss Si3N4 photonic integrated circuits with thin-film LiNbO3 through direct bonding at the wafer level, in contrast to previously demonstrated chiplet-level integration10, featuring low propagation loss of 8.5 decibels per metre, enabling narrow-linewidth lasing (intrinsic linewidth of 3 kilohertz) by self-injection locking to a laser diode. The hybrid mode of the resonator allows electro-optic laser frequency tuning at a speed of 12 × 1015 hertz per second with high linearity and low hysteresis while retaining the narrow linewidth. Using a hybrid integrated laser, we perform a proof-of-concept coherent optical ranging (FMCW LiDAR) experiment. Endowing Si3N4 photonic integrated circuits with LiNbO3 creates a platform that combines the individual advantages of thin-film LiNbO3 with those of Si3N4, which show precise lithographic control, mature manufacturing and ultralow loss11,12.

Carbonaceous dust grains seen in the first billion years of cosmic time.

Large dust reservoirs (up to approximately 108 M⊙) have been detected1-3 in galaxies out to redshift z ≃ 8, when the age of the Universe was only about 600 Myr. Generating substantial amounts of dust within such a short timescale has proven challenging for theories of dust formation4,5 and has prompted the revision of the modelling of potential sites of dust production6-8, such as the atmospheres of asymptotic giant branch stars in low-metallicity environments, supernova ejecta and the accelerated growth of grains in the interstellar medium. However, degeneracies between different evolutionary pathways remain when the total dust mass of galaxies is the only available observable. Here we report observations of the 2,175 Å dust attenuation feature, which is well known in the Milky Way and galaxies at z ≲ 3 (refs. 9-11), in the near-infrared spectra of galaxies up to z ≃ 7, corresponding to the first billion years of cosmic time. The relatively short timescale implied for the formation of carbonaceous grains giving rise to this feature12 suggests a rapid production process, possibly in Wolf-Rayet stars or supernova ejecta.

Topological lattices realized in superconducting circuit optomechanics.

Cavity optomechanics enables the control of mechanical motion through the radiation-pressure interaction1, and has contributed to the quantum control of engineered mechanical systems ranging from kilogramme-scale Laser Interferometer Gravitational-wave Observatory (LIGO) mirrors to nanomechanical systems, enabling ground-state preparation2,3, entanglement4,5, squeezing of mechanical objects6, position measurements at the standard quantum limit7 and quantum transduction8. Yet nearly all previous schemes have used single- or few-mode optomechanical systems. By contrast, new dynamics and applications are expected when using optomechanical lattices9, which enable the synthesis of non-trivial band structures, and these lattices have been actively studied in the field of circuit quantum electrodynamics10. Superconducting microwave optomechanical circuits2 are a promising platform to implement such lattices, but have been compounded by strict scaling limitations. Here we overcome this challenge and demonstrate topological microwave modes in one-dimensional circuit optomechanical chains realizing the Su-Schrieffer-Heeger model11,12. Furthermore, we realize the strained graphene model13,14 in a two-dimensional optomechanical honeycomb lattice. Exploiting the embedded optomechanical interaction, we show that it is possible to directly measure the mode functions of the hybridized modes without using any local probe15,16. This enables us to reconstruct the full underlying lattice Hamiltonian and directly measure the existing residual disorder. Such optomechanical lattices, accompanied by the measurement techniques introduced, offer an avenue to explore collective17,18, quantum many-body19 and quench20 dynamics, topological properties9,21 and, more broadly, emergent nonlinear dynamics in complex optomechanical systems with a large number of degrees of freedom22-24.

A photonic integrated continuous-travelling-wave parametric amplifier.

The ability to amplify optical signals is of pivotal importance across science and technology typically using rare-earth-doped fibres or gain media based on III-V semiconductors. A different physical process to amplify optical signals is to use the Kerr nonlinearity of optical fibres through parametric interactions1,2. Pioneering work demonstrated continuous-wave net-gain travelling-wave parametric amplification in fibres3, enabling, for example, phase-sensitive (that is, noiseless) amplification4, link span increase5, signal regeneration and nonlinear phase noise mitigation6. Despite great progress7-15, all photonic integrated circuit-based demonstrations of net parametric gain have necessitated pulsed lasers, limiting their practical use. Until now, only bulk micromachined periodically poled lithium niobate (PPLN) waveguide chips have achieved continuous-wave gain16,17, yet their integration with silicon-wafer-based photonic circuits has not been shown. Here we demonstrate a photonic-integrated-circuit-based travelling-wave optical parametric amplifier with net signal gain in the continuous-wave regime. Using ultralow-loss, dispersion-engineered, metre-long, Si3N4 photonic integrated circuits18 on a silicon chip of dimensions 5 × 5 mm2, we achieve a continuous parametric gain of 12 dB that exceeds both the on-chip optical propagation loss and fibre-chip-fibre coupling losses in the telecommunication C band. Our work demonstrates the potential of photonic-integrated-circuit-based parametric amplifiers that have lithographically controlled gain spectrum, compact footprint, resilience to optical feedback and quantum-limited performance, and can operate in the wavelength ranges from visible to mid-infrared and outside conventional rare-earth amplification bands.

Integrated photonics enables continuous-beam electron phase modulation.

Integrated photonics facilitates extensive control over fundamental light-matter interactions in manifold quantum systems including atoms1, trapped ions2,3, quantum dots4 and defect centres5. Ultrafast electron microscopy has recently made free-electron beams the subject of laser-based quantum manipulation and characterization6-11, enabling the observation of free-electron quantum walks12-14, attosecond electron pulses10,15-17 and holographic electromagnetic imaging18. Chip-based photonics19,20 promises unique applications in nanoscale quantum control and sensing but remains to be realized in electron microscopy. Here we merge integrated photonics with electron microscopy, demonstrating coherent phase modulation of a continuous electron beam using a silicon nitride microresonator. The high-finesse (Q0 ≈ 106) cavity enhancement and a waveguide designed for phase matching lead to efficient electron-light scattering at extremely low, continuous-wave optical powers. Specifically, we fully deplete the initial electron state at a cavity-coupled power of only 5.35 microwatts and generate >500 electron energy sidebands for several milliwatts. Moreover, we probe unidirectional intracavity fields with microelectronvolt resolution in electron-energy-gain spectroscopy21. The fibre-coupled photonic structures feature single-optical-mode electron-light interaction with full control over the input and output light. This approach establishes a versatile and highly efficient framework for enhanced electron beam control in the context of laser phase plates22, beam modulators and continuous-wave attosecond pulse trains23, resonantly enhanced spectroscopy24-26 and dielectric laser acceleration19,20,27. Our work introduces a universal platform for exploring free-electron quantum optics28-31, with potential future developments in strong coupling, local quantum probing and electron-photon entanglement.

Massively parallel coherent laser ranging using a soliton microcomb.

Coherent ranging, also known as frequency-modulated continuous-wave (FMCW) laser-based light detection and ranging (lidar)1 is used for long-range three-dimensional distance and velocimetry in autonomous driving2,3. FMCW lidar maps distance to frequency4,5 using frequency-chirped waveforms and simultaneously measures the Doppler shift of the reflected laser light, similar to sonar or radar6,7 and coherent detection prevents interference from sunlight and other lidar systems. However, coherent ranging has a lower acquisition speed and requires precisely chirped8 and highly coherent5 laser sources, hindering widespread use of the lidar system and impeding parallelization, compared to modern time-of-flight ranging systems that use arrays of individual lasers. Here we demonstrate a massively parallel coherent lidar scheme using an ultra-low-loss photonic chip-based soliton microcomb9. By fast chirping of the pump laser in the soliton existence range10 of a microcomb with amplitudes of up to several gigahertz and a sweep rate of up to ten megahertz, a rapid frequency change occurs in the underlying carrier waveform of the soliton pulse stream, but the pulse-to-pulse repetition rate of the soliton pulse stream is retained. As a result, the chirp from a single narrow-linewidth pump laser is transferred to all spectral comb teeth of the soliton at once, thus enabling parallelism in the FMCW lidar. Using this approach we generate 30 distinct channels, demonstrating both parallel distance and velocity measurements at an equivalent rate of three megapixels per second, with the potential to improve sampling rates beyond 150 megapixels per second and to increase the image refresh rate of the FMCW lidar by up to two orders of magnitude without deterioration of eye safety. This approach, when combined with photonic phase arrays11 based on nanophotonic gratings12, provides a technological basis for compact, massively parallel and ultrahigh-frame-rate coherent lidar systems.

Controlling free electrons with optical whispering-gallery modes.

Free-electron beams are versatile probes of microscopic structure and composition1,2, and have revolutionized atomic-scale imaging in several fields, from solid-state physics to structural biology3. Over the past decade, the manipulation and interaction of electrons with optical fields have enabled considerable progress in imaging methods4, near-field electron acceleration5,6, and four-dimensional microscopy techniques with high temporal and spatial resolution7. However, electron beams typically couple only weakly to optical excitations, and emerging applications in electron control and sensing8-11 require large enhancements using tailored fields and interactions. Here we couple a free-electron beam to a travelling-wave resonant cavity mode. The enhanced interaction with the optical whispering-gallery modes of dielectric microresonators induces a strong phase modulation on co-propagating electrons, which leads to a spectral broadening of 700 electronvolts, corresponding to the absorption and emission of hundreds of photons. By mapping the near-field interaction with ultrashort electron pulses in space and time, we trace the lifetime of the the microresonator following a femtosecond excitation and observe the spectral response of the cavity. The natural matching of free electrons to these quintessential optical modes could enable the application of integrated photonics technology in electron microscopy, with broad implications for attosecond structuring, probing quantum emitters and possible electron-light entanglement.

Monolithic piezoelectric control of soliton microcombs.

High-speed actuation of laser frequency1 is critical in applications using lasers and frequency combs2,3, and is a prerequisite for phase locking, frequency stabilization and stability transfer among optical carriers. For example, high-bandwidth feedback control of frequency combs is used in optical-frequency synthesis4, frequency division5 and optical clocks6. Soliton microcombs7,8 have emerged as chip-scale frequency comb sources, and have been used in system-level demonstrations9,10. Yet integrated microcombs using thermal heaters have limited actuation bandwidths11,12 of up to 10 kilohertz. Consequently, megahertz-bandwidth actuation and locking of microcombs have only been achieved with off-chip bulk component modulators. Here we demonstrate high-speed soliton microcomb actuation using integrated piezoelectric components13. By monolithically integrating AlN actuators14 on ultralow-loss Si3N4 photonic circuits15, we demonstrate voltage-controlled soliton initiation, tuning and stabilization with megahertz bandwidth. The AlN actuators use 300 nanowatts of power and feature bidirectional tuning, high linearity and low hysteresis. They exhibit a flat actuation response up to 1 megahertz-substantially exceeding bulk piezo tuning bandwidth-that is extendable to higher frequencies by overcoming coupling to acoustic contour modes of the chip. Via synchronous tuning of the laser and the microresonator, we exploit this ability to frequency-shift the optical comb spectrum (that is, to change the comb's carrier-envelope offset frequency) and make excursions beyond the soliton existence range. This enables a massively parallel frequency-modulated engine16,17 for lidar (light detection and ranging), with increased frequency excursion, lower power and elimination of channel distortions resulting from the soliton Raman self-frequency shift. Moreover, by modulating at a rate matching the frequency of high-overtone bulk acoustic resonances18, resonant build-up of bulk acoustic energy allows a 14-fold reduction of the required driving voltage, making it compatible with CMOS (complementary metal-oxide-semiconductor) electronics. Our approach endows soliton microcombs with integrated, ultralow-power and fast actuation, expanding the repertoire of technological applications of microcombs.

Integrated turnkey soliton microcombs.

Optical frequency combs have a wide range of applications in science and technology1. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators2-9. Such soliton microcombs10 have been applied to spectroscopy11-13, the search for exoplanets14,15, optical frequency synthesis16, time keeping17 and other areas10. In addition, the recent integration of microresonators with lasers has revealed the viability of fully chip-based soliton microcombs18,19. However, the operation of microcombs requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components, and microcombs operating at rates that are compatible with electronic circuits-as is required in nearly all comb systems-have not yet been integrated with pump lasers because of their high power requirements. Here we experimentally demonstrate and theoretically describe a turnkey operation regime for soliton microcombs co-integrated with a pump laser. We show the appearance of an operating point at which solitons are immediately generated by turning the pump laser on, thereby eliminating the need for photonic and electronic control circuitry. These features are combined with high-quality-factor Si3N4 resonators to provide microcombs with repetition frequencies as low as 15 gigahertz that are fully integrated into an industry standard (butterfly) package, thereby offering compelling advantages for high-volume production.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Synthetic anaplerotic modules for the direct synthesis of complex molecules from CO2.

Anaplerosis is an essential feature of metabolism that allows the continuous operation of natural metabolic networks, such as the citric acid cycle, by constantly replenishing drained intermediates. However, this concept has not been applied to synthetic in vitro metabolic networks, thus far. Here we used anaplerotic strategies to directly access the core sequence of the CETCH cycle, a new-to-nature in vitro CO2-fixation pathway that features several C3-C5 biosynthetic precursors. We drafted four different anaplerotic modules that use CO2 to replenish the CETCH cycle's intermediates and validated our designs by producing 6-deoxyerythronolide B (6-DEB), the C21-macrolide backbone of erythromycin. Our best design allowed the carbon-positive synthesis of 6-DEB via 54 enzymatic reactions in vitro at yields comparable to those with isolated 6-DEB polyketide synthase (DEBS). Our work showcases how new-to-nature anaplerotic modules can be designed and tailored to enhance and expand the synthetic capabilities of complex catalytic in vitro reaction networks.

The dual role of a highly structured RNA (the S fragment) in the replication of foot-and-mouth disease virus.

Secondary and tertiary RNA structures play key roles in genome replication of single-stranded positive sense RNA viruses. Complex, functional structures are particularly abundant in the untranslated regions of picornaviruses, where they are involved in initiation of translation, priming of new strand synthesis and genome circularization. The 5' UTR of foot-and-mouth disease virus (FMDV) is predicted to include a c. 360 nucleotide-long stem-loop, termed the short (S) fragment. This structure is highly conserved and essential for viral replication, but the precise function(s) are unclear. Here, we used selective 2' hydroxyl acetylation analyzed by primer extension (SHAPE) to experimentally determine aspects of the structure, alongside comparative genomic analyses to confirm structure conservation from a wide range of field isolates. To examine its role in virus replication in cell culture, we introduced a series of deletions to the distal and proximal regions of the stem-loop. These truncations affected genome replication in a size-dependent and, in some cases, host cell-dependent manner. Furthermore, during the passage of viruses incorporating the largest tolerated deletion from the proximal region of the S fragment stem-loop, an additional mutation was selected in the viral RNA-dependent RNA polymerase, 3Dpol. These data suggest that the S fragment and 3Dpol interact in the formation of the FMDV replication complex.

Molecular biology for green recovery-A call for action.

Molecular biology holds a vast potential for tackling climate change and biodiversity loss. Yet, it is largely absent from the current strategies. We call for a community-wide action to bring molecular biology to the forefront of climate change solutions.

Enzymatic Conversion of CO2: From Natural to Artificial Utilization.

Enzymatic carbon dioxide fixation is one of the most important metabolic reactions as it allows the capture of inorganic carbon from the atmosphere and its conversion into organic biomass. However, due to the often unfavorable thermodynamics and the difficulties associated with the utilization of CO2, a gaseous substrate that is found in comparatively low concentrations in the atmosphere, such reactions remain challenging for biotechnological applications. Nature has tackled these problems by evolution of dedicated CO2-fixing enzymes, i.e., carboxylases, and embedding them in complex metabolic pathways. Biotechnology employs such carboxylating and decarboxylating enzymes for the carboxylation of aromatic and aliphatic substrates either by embedding them into more complex reaction cascades or by shifting the reaction equilibrium via reaction engineering. This review aims to provide an overview of natural CO2-fixing enzymes and their mechanistic similarities. We also discuss biocatalytic applications of carboxylases and decarboxylases for the synthesis of valuable products and provide a separate summary of strategies to improve the efficiency of such processes. We briefly summarize natural CO2 fixation pathways, provide a roadmap for the design and implementation of artificial carbon fixation pathways, and highlight examples of biocatalytic cascades involving carboxylases. Additionally, we suggest that biochemical utilization of reduced CO2 derivates, such as formate or methanol, represents a suitable alternative to direct use of CO2 and provide several examples. Our discussion closes with a techno-economic perspective on enzymatic CO2 fixation and its potential to reduce CO2 emissions.