An unexpected hydratase synthesizes the green light-absorbing pigment fucoxanthin.

The ketocarotenoid fucoxanthin and its derivatives can absorb blue-green light enriched in marine environments. Fucoxanthin is widely adopted by phytoplankton species as a main light-harvesting pigment, in contrast to land plants that primarily employ chlorophylls. Despite its supreme abundance in the oceans, the last steps of fucoxanthin biosynthesis have remained elusive. Here, we identified the carotenoid isomerase-like protein CRTISO5 as the diatom fucoxanthin synthase that is related to the carotenoid cis-trans isomerase CRTISO from land plants but harbors unexpected enzymatic activity. A crtiso5 knockout mutant in the model diatom Phaeodactylum tricornutum completely lacked fucoxanthin and accumulated the acetylenic carotenoid phaneroxanthin. Recombinant CRTISO5 converted phaneroxanthin into fucoxanthin in vitro by hydrating its carbon-carbon triple bond, instead of functioning as an isomerase. Molecular docking and mutational analyses revealed residues essential for this activity. Furthermore, a photophysiological characterization of the crtiso5 mutant revealed a major structural and functional role of fucoxanthin in photosynthetic pigment-protein complexes of diatoms. As CRTISO5 hydrates an internal alkyne physiologically, the enzyme has unique potential for biocatalytic applications. The discovery of CRTISO5 illustrates how neofunctionalization leads to major diversification events in evolution of photosynthetic mechanisms and the prominent brown coloration of most marine photosynthetic eukaryotes.

Green diatom mutants reveal an intricate biosynthetic pathway of fucoxanthin.

Fucoxanthin is a major light-harvesting pigment in ecologically important algae such as diatoms, haptophytes, and brown algae (Phaeophyceae). Therefore, it is a major driver of global primary productivity. Species of these algal groups are brown colored because the high amounts of fucoxanthin bound to the proteins of their photosynthetic machineries enable efficient absorption of green light. While the structure of these fucoxanthin-chlorophyll proteins has recently been resolved, the biosynthetic pathway of fucoxanthin is still unknown. Here, we identified two enzymes central to this pathway by generating corresponding knockout mutants of the diatom Phaeodactylum tricornutum that are green due to the lack of fucoxanthin. Complementation of the mutants with the native genes or orthologs from haptophytes restored fucoxanthin biosynthesis. We propose a complete biosynthetic path to fucoxanthin in diatoms and haptophytes based on the carotenoid intermediates identified in the mutants and in vitro biochemical assays. It is substantially more complex than anticipated and reveals diadinoxanthin metabolism as the central regulatory hub connecting the photoprotective xanthophyll cycle and the formation of fucoxanthin. Moreover, our data show that the pathway evolved by repeated duplication and neofunctionalization of genes for the xanthophyll cycle enzymes violaxanthin de-epoxidase and zeaxanthin epoxidase. Brown algae lack diadinoxanthin and the genes described here and instead use an alternative pathway predicted to involve fewer enzymes. Our work represents a major step forward in elucidating the biosynthesis of fucoxanthin and understanding the evolution, biogenesis, and regulation of the photosynthetic machinery in algae.

Characterizing compensatory mechanisms in the absence of photoprotective qE in Chlamydomonas reinhardtii.

Rapid fluctuations in the quantity and quality of natural light expose photosynthetic organisms to conditions when the capacity to utilize absorbed quanta is insufficient. These conditions can result in the production of reactive oxygen species and photooxidative damage. Non-photochemical quenching (NPQ) and alternative electron transport are the two most prominent mechanisms which synergistically function to minimize the overreduction of photosystems. In the green alga Chlamydomonas reinhardtii, the stress-related light-harvesting complex (LHCSR) is a required component for the rapid induction and relaxation of NPQ in the light-harvesting antenna. Here, we use simultaneous chlorophyll fluorescence and oxygen exchange measurements to characterize the acclimation of the Chlamydomonas LHCSR-less mutant (npq4lhcsr1) to saturating light conditions. We demonstrate that, in the absence of NPQ, Chlamydomonas does not acclimate to sinusoidal light through increased light-dependent oxygen consumption. We also show that the npq4lhcsr1 mutant has an increased sink capacity downstream of PSI and this energy flow is likely facilitated by cyclic electron transport. Furthermore, we show that the timing of additions of mitochondrial inhibitors has a major influence on plastid/mitochondrial coupling experiments.

A Chlorophyte Alga Utilizes Alternative Electron Transport for Primary Photoprotection.

The green alga Desmodesmus armatus is an emerging biofuel platform that produces high amounts of lipids and biomass in mass culture. We observed D. armatus in light-limiting, excess-light, and sinusoidal-light environments to investigate its photoacclimation behaviors and the mechanisms by which it dissipates excess energy. Chlorophyll a/b ratios and the functional absorption cross section of PSII suggested a constitutively small light-harvesting antenna size relative to other green algae. In situ and ex situ measurements of photo-physiology revealed that nonphotochemical quenching is not a significant contributor to photoprotection; however, cells do not suffer substantial photoinhibition despite its near absence. We performed membrane inlet mass spectrometry analysis to show that D. armatus has a very high capacity for alternative electron transport (AET) measured as light-dependent oxygen consumption. Up to 90% of electrons generated at PSII can be dissipated by AET in a water-water cycle during growth in rapidly fluctuating light environments, like those found in industrial-scale photobioreactors. This work highlights the diversity of photoprotective mechanisms present in algal systems, indicating that nonphotochemical quenching is not necessarily required for effective photoprotection in some algae, and suggests that engineering AET may be an attractive target for increasing the biomass productivity of some strains.

The Fluctuating Cell-Specific Light Environment and Its Effects on Cyanobacterial Physiology.

Individual cells of cyanobacteria or algae are supplied with light in a highly irregular fashion when grown in industrial-scale photobioreactors (PBRs). These conditions coincide with significant reductions in growth rate compared to the static light environments commonly used in laboratory experiments. We grew a dense culture of the model cyanobacterium Synechocystis sp. PCC 6803 under a sinusoidal light regime in a bench-top PBR (the Phenometrics environmental PBR [ePBR]). We developed a computational fluid dynamics model of the ePBR, which predicted that individual cells experienced rapid fluctuations (∼6 s) between 2,000 and <1 µmol photons m-2 s-1, caused by vertical mixing and self-shading. The daily average light exposure of a single cell was 180 µmol photons m-2 s-1 Physiological measurements across the day showed no in situ occurrence of nonphotochemical quenching, and there was no significant photoinhibition. An ex situ experiment showed that up to 50% of electrons derived from PSII were diverted to alternative electron transport in a rapidly changing light environment modeled after the ePBR. Collectively, our results suggest that modification of nonphotochemical quenching may not increase cyanobacterial productivity in PBRs with rapidly changing light. Instead, tuning the rate of alternative electron transport and increasing the processing rates of electrons downstream of PSI are potential avenues to enhance productivity. The approach presented here could be used as a template to investigate the photophysiology of any aquatic photoautotroph in a natural or industrially relevant mixing regime.

A Program for Iron Economy during Deficiency Targets Specific Fe Proteins.

Iron (Fe) is an essential element for plants, utilized in nearly every cellular process. Because the adjustment of uptake under Fe limitation cannot satisfy all demands, plants need to acclimate their physiology and biochemistry, especially in their chloroplasts, which have a high demand for Fe. To investigate if a program exists for the utilization of Fe under deficiency, we analyzed how hydroponically grown Arabidopsis (Arabidopsis thaliana) adjusts its physiology and Fe protein composition in vegetative photosynthetic tissue during Fe deficiency. Fe deficiency first affected photosynthetic electron transport with concomitant reductions in carbon assimilation and biomass production when effects on respiration were not yet significant. Photosynthetic electron transport function and protein levels of Fe-dependent enzymes were fully recovered upon Fe resupply, indicating that the Fe depletion stress did not cause irreversible secondary damage. At the protein level, ferredoxin, the cytochrome-b6f complex, and Fe-containing enzymes of the plastid sulfur assimilation pathway were major targets of Fe deficiency, whereas other Fe-dependent functions were relatively less affected. In coordination, SufA and SufB, two proteins of the plastid Fe-sulfur cofactor assembly pathway, were also diminished early by Fe depletion. Iron depletion reduced mRNA levels for the majority of the affected proteins, indicating that loss of enzyme was not just due to lack of Fe cofactors. SufB and ferredoxin were early targets of transcript down-regulation. The data reveal a hierarchy for Fe utilization in photosynthetic tissue and indicate that a program is in place to acclimate to impending Fe deficiency.

The anastomotic leak triad: preoperative patient characteristics, intraoperative risk factors, and postoperative outcomes.

BACKGROUND: The aim of this study was to determine perioperative risk factors associated with anastomotic leak (AL) after minimally invasive esophagectomy (MIE) and its association with cancer recurrence and overall survival. METHODS: This retrospective observational study of electronic health record data included patients who underwent MIE for esophageal cancer between September 2013 and July 2023 at a tertiary center. The primary outcome was AL after esophagectomy, whereas the secondary outcomes included time to cancer recurrence and overall survival. Perioperative patient factors were evaluated to determine their associations with the primary and the secondary outcomes. Propensity score-matched logistic regression assessed the associations between perioperative factors and AL. Kaplan-Meier survival curves compared cancer recurrence and overall survival by AL. RESULTS: A total of 251 consecutive patients with esophageal cancer were included in the analysis; 15 (6%) developed AL. Anemia, hospital complications, hospital length of stay, and 30-day readmissions significantly differed from those with and without AL (P = .037, <.001, <.001, and.016, respectively). Moreover, 30- and 90-day mortality were not statistically affected by the presence of AL (P = .417 and 0.456, respectively). Logistic regression modeling showed drug history and anemia were significantly associated with AL (P = .022 and.011, respectively). The presence of AL did not significantly impact cancer recurrence or overall survival (P = .439 and.301, respectively). CONCLUSION: The etiology of AL is multifactorial. Moreover, AL is significantly associated with drug history, preoperative anemia, hospital length of stay, and 30-day readmissions, but it was not significantly associated with 30- or 90-day mortality, cancer recurrence, or overall survival. Patients should be optimized before undergoing MIE with special consideration for correcting anemia. Ongoing research is needed to identify more modifiable risk factors to minimize AL development and its associated morbidity.

Intraoperative fluid management is not predictive of AKI in major pancreatic surgery: a retrospective cohort study.

BACKGROUND: Pancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This investigation evaluated the impact of intraoperative volume administration, vasopressor therapy, and blood pressure management on the primary outcome of AKI and the secondary outcome of a CR-POPF after pancreatic surgery. METHODS: This retrospective single-center cohort investigated 200 consecutive pancreatic surgeries (January 2018-December 2021). Patients were categorized for the presence/absence of AKI (Kidney Disease Improving Global Outcomes) and CR-POPF. After univariate analysis, multivariable models were constructed to control for the univariate cofactor differences in the primary and secondary outcomes. RESULTS: AKI was identified in 20 patients (10%) with significant univariate differences in demographics (body mass index and gender), comorbidities, indices of chronic renal insufficiency, and an increased AKI Risk score. Surgical characteristics, intraoperative fluid, vasopressor, and blood pressure management were similar in patients with and without AKI. Patients with AKI had increased blood loss, lower urine output, and packed red blood cell administration. After multivariate analysis, male gender (OR = 7.9, 95% C.I. 1.8-35.1) and the AKI Risk score (OR = 6.3, 95% C.I. 2.4-16.4) were associated with the development of AKI (p < 0.001). Intraoperative and postoperative volume, vasopressor administration, and intraoperative hypotension had no significant impact in the multivariate analysis. CR-POPF occurred in 23 patients (11.9%) with no significant contributing factors in the multivariate analysis. Patients who developed AKI or a CR-POPF had an increase in surgical complications, length of stay, discharge to a skilled nursing facility, and mortality. CONCLUSION: In this analysis, intraoperative volume administration, vasopressor therapy, and a blood pressure < 55 mmHg for more than 10 min were not associated with an increased risk of AKI. After multivariate analysis, male gender and an elevated AKI Risk score were associated with an increased likelihood of AKI.

Polyphosphate kinase deletion increases laboratory productivity in cyanobacteria.

Identification and manipulation of cellular energy regulation mechanisms may be a strategy to increase productivity in photosynthetic organisms. This work tests the hypothesis that polyphosphate synthesis and degradation play a role in energy management by storing or dissipating energy in the form of ATP. A polyphosphate kinase (ppk) knock-out strain unable to synthesize polyphosphate was generated in the cyanobacterium Synechocystis sp. PCC 6803. This mutant strain demonstrated higher ATP levels and faster growth than the wildtype strain in high-carbon conditions and had a growth defect under multiple stress conditions. In a strain that combined ppk deletion with heterologous expression of ethylene-forming enzyme, higher ethylene productivity was observed than in the wildtype background. These results support the role of polyphosphate synthesis and degradation as an energy regulation mechanism and suggest that such mechanisms may be effective targets in biocontainment design.

Manipulation of glycogen and sucrose synthesis increases photosynthetic productivity in cyanobacteria.

Photosynthetic productivity is limited by low energy conversion efficiency in naturally evolved photosynthetic organisms, via multiple mechanisms that are not fully understood. Here we show evidence that extends recent findings that cyanobacteria use "futile" cycles in the synthesis and degradation of carbon compounds to dissipate ATP. Reduction of the glycogen cycle or the sucrose cycle in the model cyanobacterium Synechocystis 6803 led to redirection of cellular energy toward faster growth under simulated outdoor light conditions in photobioreactors that was accompanied by higher energy charge [concentration ratio of ATP/(ATP + ADP)]. Such manipulation of energy metabolism may have potential in engineering microalgal chassis cells to increase productivity of biomass or target metabolites.

Isolation of phosphorus-hyperaccumulating microalgae from revolving algal biofilm (RAB) wastewater treatment systems.

Excess phosphorus (P) in wastewater effluent poses a serious threat to aquatic ecosystems and can spur harmful algal blooms. Revolving algal biofilm (RAB) systems are an emerging technology to recover P from wastewater before discharge into aquatic ecosystems. In RAB systems, a community of microalgae take up and store wastewater P as polyphosphate as they grow in a partially submerged revolving biofilm, which may then be harvested and dried for use as fertilizer in lieu of mined phosphate rock. In this work, we isolated and characterized a total of 101 microalgae strains from active RAB systems across the US Midwest, including 82 green algae, 9 diatoms, and 10 cyanobacteria. Strains were identified by microscopy and 16S/18S ribosomal DNA sequencing, cryopreserved, and screened for elevated P content (as polyphosphate). Seven isolated strains possessed at least 50% more polyphosphate by cell dry weight than a microalgae consortium from a RAB system, with the top strain accumulating nearly threefold more polyphosphate. These top P-hyperaccumulating strains include the green alga Chlamydomonas pulvinata TCF-48 g and the diatoms Eolimna minima TCF-3d and Craticula molestiformis TCF-8d, possessing 11.4, 12.7, and 14.0% polyphosphate by cell dry weight, respectively. As a preliminary test of strain application for recovering P, Chlamydomonas pulvinata TCF-48 g was reinoculated into a bench-scale RAB system containing Bold basal medium. The strain successfully recolonized the system and recovered twofold more P from the medium than a microalgae consortium from a RAB system treating municipal wastewater. These isolated P-hyperaccumulating microalgae may have broad applications in resource recovery from various waste streams, including improving P removal from wastewater.

Functional screening of amplification outlier oncogenes in organoid models of early tumorigenesis.

Somatic copy number gains are pervasive across cancer types, yet their roles in oncogenesis are insufficiently evaluated. This inadequacy is partly due to copy gains spanning large chromosomal regions, obscuring causal loci. Here, we employed organoid modeling to evaluate candidate oncogenic loci identified via integrative computational analysis of extreme copy gains overlapping with extreme expression dysregulation in The Cancer Genome Atlas. Subsets of "outlier" candidates were contextually screened as tissue-specific cDNA lentiviral libraries within cognate esophagus, oral cavity, colon, stomach, pancreas, and lung organoids bearing initial oncogenic mutations. Iterative analysis nominated the kinase DYRK2 at 12q15 as an amplified head and neck squamous carcinoma oncogene in p53-/- oral mucosal organoids. Similarly, FGF3, amplified at 11q13 in 41% of esophageal squamous carcinomas, promoted p53-/- esophageal organoid growth reversible by small molecule and soluble receptor antagonism of FGFRs. Our studies establish organoid-based contextual screening of candidate genomic drivers, enabling functional evaluation during early tumorigenesis.

c-Jun N-terminal kinase 2 (JNK2) enhances cell migration through epidermal growth factor substrate 8 (EPS8).

Membrane-bound receptors induce biochemical signals to remodel the actin cytoskeleton and mediate cell motility. In association with receptor tyrosine kinases, several downstream mitogen-induced kinases facilitate cell migration. Here, we show a role for c-Jun N-terminal kinase 2 (JNK2) in promoting mammary cancer cell migration through inhibition of epidermal growth factor substrate 8 (EPS8) expression, a key regulator of EGF receptor (R) signaling and trafficking. Using jnk2(-/-) mice, we found that EPS8 expression is higher in polyoma middle T antigen (PyVMT)jnk2(-/-) mammary tumors and jnk2(-/-) mammary glands compared with the respective jnk2(+/+) controls. The inverse relationship between the jnk2 and eps8 expression was also associated with cancer progression in that patients with basal-type breast tumors expressing high jnk2 and low eps8 experienced poor disease-free survival. In mammary tumor cell lines, the absence of jnk2 greatly reduces cell migration that is rescued by EPS8 knockdown. Subsequent studies show that JNK2 enhances formation of the EPS8-Abi-1-Sos-1 complex to augment EGFR activation of Akt and ERK, whereas the absence of JNK2 promotes ESP8/RN-Tre association to inhibit endocytotic trafficking of the EGFR. Together, these studies unveil a critical role for JNK2 and EPS8 in receptor tyrosine kinase signaling and trafficking to convey distinctly different effects on cell migration.

Identifying the status of genetic lesions in cancer clinical trial documents using machine learning.

BACKGROUND: Many cancer clinical trials now specify the particular status of a genetic lesion in a patient's tumor in the inclusion or exclusion criteria for trial enrollment. To facilitate search and identification of gene-associated clinical trials by potential participants and clinicians, it is important to develop automated methods to identify genetic information from narrative trial documents. METHODS: We developed a two-stage classification method to identify genes and genetic lesion statuses in clinical trial documents extracted from the National Cancer Institute's (NCI's) Physician Data Query (PDQ) cancer clinical trial database. The method consists of two steps: 1) to distinguish gene entities from non-gene entities such as English words; and 2) to determine whether and which genetic lesion status is associated with an identified gene entity. We developed and evaluated the performance of the method using a manually annotated data set containing 1,143 instances of the eight most frequently mentioned genes in cancer clinical trials. In addition, we applied the classifier to a real-world task of cancer trial annotation and evaluated its performance using a larger sample size (4,013 instances from 249 distinct human gene symbols detected from 250 trials). RESULTS: Our evaluation using a manually annotated data set showed that the two-stage classifier outperformed the single-stage classifier and achieved the best average accuracy of 83.7% for the eight most frequently mentioned genes when optimized feature sets were used. It also showed better generalizability when we applied the two-stage classifier trained on one set of genes to another independent gene. When a gene-neutral, two-stage classifier was applied to the real-world task of cancer trial annotation, it achieved a highest accuracy of 89.8%, demonstrating the feasibility of developing a gene-neutral classifier for this task. CONCLUSIONS: We presented a machine learning-based approach to detect gene entities and the genetic lesion statuses from clinical trial documents and demonstrated its use in cancer trial annotation. Such methods would be valuable for building information retrieval tools targeting gene-associated clinical trials.

Retrofitting the genome: L1 extinction follows endogenous retroviral expansion in a group of muroid rodents.

Long interspersed nuclear element 1 (LINE-1; L1) retrotransposons are the most common retroelements in mammalian genomes. Unlike individual families of endogenous retroviruses (ERVs), they have remained active throughout the mammalian radiation and are responsible for most of the retroelement movement and much genome rearrangement within mammals. They can be viewed as occupying a substantial niche within mammalian genomes. Our previous demonstration that L1s and B1 short interspersed nuclear elements (SINEs) are inactive in a group of South American rodents led us to ask if other elements have amplified to fill the empty niche. We identified a novel and highly active family of ERVs (mysTR). To determine whether loss of L1 activity was correlated with expansion of mysTR, we examined mysTR activity in four South American rodent species that have lost L1 and B1 activity and four sister species with active L1s. The copy number of recent mysTR insertions was extremely high, with an average of 4,200 copies per genome. High copy numbers exist in both L1-active and L1-extinct species, so the mysTR expansion appears to have preceded the loss of both SINE and L1 activity rather than to have filled an empty niche created by their loss. It may be coincidental that two unusual genomic events--loss of L1 activity and massive expansion of an ERV family--occur in the same group of mammals. Alternatively, it is possible that this large ERV expansion set the stage for L1 extinction.

Supporting tool suite for production proteomics.

SUMMARY: The large amount of data produced by proteomics experiments requires effective bioinformatics tools for the integration of data management and data analysis. Here we introduce a suite of tools developed at Vanderbilt University to support production proteomics. We present the Backup Utility Service tool for automated instrument file backup and the ScanSifter tool for data conversion. We also describe a queuing system to coordinate identification pipelines and the File Collector tool for batch copying analytical results. These tools are individually useful but collectively reinforce each other. They are particularly valuable for proteomics core facilities or research institutions that need to manage multiple mass spectrometers. With minor changes, they could support other types of biomolecular resource facilities.

Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study.

BACKGROUND: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10. RESULTS: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK (p = 0.01), EGFR (p < 0.01), and TP53 (p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21-0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21-0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. CONCLUSIONS: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.

Loss of LINE-1 activity in the megabats.

LINE-1 (L1) retrotransposons are the most abundant type of mammalian retroelement. They have profound effects on genome plasticity and have been proposed to fulfill essential host functions, yet it remains unclear where they lie on the spectrum from parasitism to mutualism. Their ubiquity makes it difficult to determine the extent of their effects on genome evolution and gene expression because of the relative dearth of animal models lacking L1 activity. We have isolated L1 sequences from 11 megabat species by a method that enriches for recently inserted L1s and have done a bioinformatic examination of L1 sequences from a 12th species whose genome was recently shotgun sequenced. An L1 extinction event appears to have occurred at least 24 million years ago (MYA) in an ancestor of the megabats. The ancestor was unusual in having maintained two highly divergent long-term L1 lineages with different levels of activity, which appear, on an evolutionary scale, to have simultaneously lost that activity. These megabat species can serve as new animal models to ask what effect loss of L1 activity has on mammalian genome evolution and gene expression.

A mutant of Chlamydomonas without LHCSR maintains high rates of photosynthesis, but has reduced cell division rates in sinusoidal light conditions.

The LHCSR protein belongs to the light harvesting complex family of pigment-binding proteins found in oxygenic photoautotrophs. Previous studies have shown that this complex is required for the rapid induction and relaxation of excess light energy dissipation in a wide range of eukaryotic algae and moss. The ability of cells to rapidly regulate light harvesting between this dissipation state and one favoring photochemistry is believed to be important for reducing oxidative stress and maintaining high photosynthetic efficiency in a rapidly changing light environment. We found that a mutant of Chlamydomonas reinhardtii lacking LHCSR, npq4lhcsr1, displays minimal photoinhibition of photosystem II and minimal inhibition of short term oxygen evolution when grown in constant excess light compared to a wild type strain. We also investigated the impact of no LHCSR during growth in a sinusoidal light regime, which mimics daily changes in photosynthetically active radiation. The absence of LHCSR correlated with a slight reduction in the quantum efficiency of photosystem II and a stimulation of the maximal rates of photosynthesis compared to wild type. However, there was no reduction in carbon accumulation during the day. Another novel finding was that npq4lhcsr1 cultures underwent fewer divisions at night, reducing the overall growth rate compared to the wild type. Our results show that the rapid regulation of light harvesting mediated by LHCSR is required for high growth rates, but it is not required for efficient carbon accumulation during the day in a sinusoidal light environment. This finding has direct implications for engineering strategies directed at increasing photosynthetic productivity in mass cultures.