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Abstract The red algaAsparagopsis taxiformishas recently been recognized for its unique ability to significantly reduce methane emissions from ruminant animals when fed in small quantities. The main obstacle in using this seaweed as a methane‐mitigating feed supplement is the lack of commercially available biomass. Little is known about how best to grow this red alga on a commercial scale, as there are few published studies that have investigated the factors that influence growth, physiology, and overall performance. This study examined the effects of temperature and CO₂enrichment on the growth, photophysiology, and concentration of bromoform, the secondary metabolite largely responsible for methane reduction inA. taxiformis. A series of single and multifactor closed culture experiments were conducted onA. taxiformiscollected, isolated, and cultured from populations in Southern California. We identified the optimal temperature range to be between 22 and 26°C, with significant short‐term stress observed below 15°C and above 26°C. Carbon dioxide addition resulted in increased performance, when accounting for growth per CO₂use. In general, we observed the highest bromoform concentrations in algae with the highest growth rates, but these results varied among experiments. These findings indicate that through environmental control and by addressing limiting resources, significant increases in biomass production and quality can be achieved. 

Artificial intelligence-driven advances in protein structure prediction in recent years have raised the question: has the protein structure-prediction problem been solved? Here, with a focus on nonglobular proteins, we highlight the many strengths and potential weaknesses of DeepMind’s AlphaFold2 in the context of its biological and therapeutic applications. We summarize the subtleties associated with evaluation of AlphaFold2 model quality and reliability using the predicted local distance difference test (pLDDT) and predicted aligned error (PAE) values. We highlight various classes of proteins that AlphaFold2 can be applied to and the caveats involved. Concrete examples of how AlphaFold2 models can be integrated with experimental data in the form of small-angle X-ray scattering (SAXS), solution NMR, cryo-electron microscopy (cryo-EM) and X-ray diffraction are discussed. Finally, we highlight the need to move beyond structure prediction of rigid, static structural snapshots toward conformational ensembles and alternate biologically relevant states. The overarching theme is that careful consideration is due when using AlphaFold2-generated models to generate testable hypotheses and structural models, rather than treating predicted models as de facto ground truth structures. 

Microbulbiferis a genus of halophilic bacteria that are commonly detected in the commensal marine microbiomes. These bacteria have been recognized for their ability to degrade polysaccharides and other polymeric materials. Increasingly,Microbulbifergenomes indicate these bacteria to be an untapped reservoir for novel natural product discovery and biosynthetic novelty. In this review, we summarize the distribution ofMicrobulbiferbacteria, activities of the various polymer degrading enzymes that these bacteria produce, and an up-to-date summary of the natural products that have been isolated fromMicrobulbiferstrains. We argue that these bacteria have been hiding in plain sight, and contemporary efforts into their genome and metabolome mining are going to lead to a proliferation ofMicrobulbifer-derived natural products in the future. We also describe, where possible, the ecological interactions of these bacteria in marine microbiomes. 

Sponges (Porifera) contain many peptide-specialized metabolites with potent biological activities and significant roles in shaping marine ecology. It is well established that symbiotic bacteria produce bioactive “sponge” peptides, both on the ribosome (RiPPs) and nonribosomally. Here, we demonstrate that sponges themselves also produce many bioactive macrocyclic peptides, such as phakellistatins and related proline-rich macrocyclic peptides (PRMPs). Using theStylissa carterisponge transcriptome, methods were developed to find sequences encoding 46 distinct RiPP-type core peptides, of which ten encoded previously identified PRMP sequences. With this basis set, the genome and transcriptome of the spongeAxinella corrugatawas interrogated to find 35 PRMP precursor peptides encoding 31 unique core peptide sequences. At least 11 of these produced cyclic peptides that were present in the sponge and could be characterized by mass spectrometry, including stylissamides A-D and seven previously undescribed compounds. Precursor peptides were encoded in theA. corrugatagenome, confirming their animal origin. The peptides contained signal peptide sequences and highly repetitive recognition sequence-core peptide elements with up to 25 PRMP copies in a single precursor. In comparison to sponges without PRMPs, PRMP sponges are incredibly enriched in potentially secreted polypeptides, with >23,000 individual signal peptide encoding genes found in a single transcriptome. The similarities between PRMP biosynthetic genes and neuropeptides in terms of their biosynthetic logic suggest a fundamental biology linked to circular peptides, possibly indicating a widespread and underappreciated diversity of signaling peptide post-translational modifications across the animal kingdom. 

The inclusion Asparagopsis spp. into the diet of ruminant animals has produced compelling data regarding the mitigation of agricultural methane emissions. This reduction is achieved via the action of brominated halogenated compounds, predominantly bromoform, which act to inhibit methanogenic enzymes in ruminant digestion. As such, there is great interest in the mass cultivation of Asparagopsis for use as a dietary supplement for livestock. However, data are still lacking on the basic biology of Asparagopsis relating to factors that influence the synthesis of bromoform, the key bioactive compound of interest. One of the two precursors for bromoform biosynthesis is hydrogen peroxide, while the other is bromide, a naturally occurring ion in seawater. Hydrogen peroxide is generated internally within the alga and can be stimulated by abiotic stress. Currently, the influence of temperature and external hydrogen peroxide addition on bromoform dynamics have been explored. The aim of this study is to explore how the stimulation of hydrogen peroxide by the application of light stress influences the dynamics of bromoform precursor uptake and production, as well as how this may drive changes in bromoform concentration and the persistence of gland cells, the cellular structures where bromoform is stored. While provision of light stress significantly stimulated an increase in hydrogen peroxide production, bromide dynamics were also significantly influenced, resulting in net bromide release, rather than uptake. Further, bromoform concentrations in algal tissue immediately declined after exposure to high light, from 4.5% to 2% (dry weight), while gland cell abundance declined from 95% to around 60%. Here we present data for dramatic alterations in bromoform dynamics after exposure to moderate increases in light intensity. These findings are strongly applicable to commercial Asparagopsis cultivation and will contribute to optimising algal quality during cultivation and harvest.