Journal of Industrial Microbiology & Biotechnology最新文献

Genkwanin has various significant roles in nutrition, biomedicine, and pharmaceutical biology. Previously, this compound was chiefly produced by plant-originated extraction or chemical synthesis. However, due to increasing concern and demand for safe food and environmental issues, the biotechnological production of genkwanin and other bioactive compounds based on safe, cheap, and renewable substrates has gained much interest. This paper described recombinant Escherichia coli-based co-culture engineering that was reconstructed for the de novo production of genkwanin from d-glucose. The artificial genkwanin biosynthetic chain was divided into 2 modules in which the upstream strain contained the genes for synthesizing p-coumaric acid from d-glucose, and the downstream module contained a gene cluster that produced the precursor apigenin and the final product, genkwanin. The Box-Behnken design, a response surface methodology, was used to empirically model the production of genkwanin and optimize its productivity. As a result, the application of the designed co-culture improved the genkwanin production by 48.8 ± 1.3 mg/L or 1.7-fold compared to the monoculture. In addition, the scale-up of genkwanin bioproduction by a bioreactor resulted in 68.5 ± 1.9 mg/L at a 48 hr time point. The combination of metabolic engineering and fermentation technology was therefore a very efficient and applicable approach to enhance the production of other bioactive compounds.

Exposure to ultraviolet (UV) rays is a known risk factor for skin cancer, which can be notably mitigated through the application of sun care products. However, escalating concerns regarding the adverse health and environmental impacts of synthetic anti-UV chemicals underscore a pressing need for the development of biodegradable and eco-friendly sunscreen ingredients. Mycosporine-like amino acids (MAAs) represent a family of water-soluble anti-UV natural products synthesized by various organisms. These compounds can provide a two-pronged strategy for sun protection as they not only exhibit a superior UV absorption profile but also possess the potential to alleviate UV-induced oxidative stresses. Nevertheless, the widespread incorporation of MAAs in sun protection products is hindered by supply constraints. Delving into the biosynthetic pathways of MAAs can offer innovative strategies to overcome this limitation. Here, we review recent progress in MAA biosynthesis, with an emphasis on key biosynthetic enzymes, including the dehydroquinate synthase homolog MysA, the adenosine triphosphate (ATP)-grasp ligases MysC and MysD, and the nonribosomal peptide synthetase (NRPS)-like enzyme MysE. Additionally, we discuss recently discovered MAA tailoring enzymes. The enhanced understanding of the MAA biosynthesis paves the way for not only facilitating the supply of MAA analogs but also for exploring the evolution of this unique family of natural sunscreens.

One-sentence summary: This review discusses the role of mycosporine-like amino acids (MAAs) as potent natural sunscreens and delves into recent progress in their biosynthesis.

Waste plastic presently accumulates in landfills or the environment. While natural microbial metabolisms can degrade plastic polymers, biodegradation of plastic is very slow. This study demonstrates that chemical deconstruction of polyethylene terephthalate (PET) with ammonium hydroxide can replace the rate limiting step (depolymerization) and by producing plastic-derived terephthalic acid and terephthalic acid monoamide. The deconstructed PET (DCPET) is neutralized with phosphoric acid prior to bioprocessing, resulting in a product containing biologically accessible nitrogen and phosphorus from the process reactants. Three microbial consortia obtained from compost and sediment degraded DCPET in ultrapure water and scavenged river water without addition of nutrients. No statistically significant difference was observed in growth rate compared to communities grown on DCPET in minimal culture medium. The consortia were dominated by Rhodococcus spp., Hydrogenophaga spp., and many lower abundance genera. All taxa were related to species known to degrade aromatic compounds. Microbial consortia are known to confer flexibility in processing diverse substrates. To highlight this, we also demonstrate that two microbial consortia can grow on similarly deconstructed polyesters, polyamides, and polyurethanes in water instead of medium. Our findings suggest that microbial communities may enable flexible bioprocessing of mixed plastic wastes when coupled with chemical deconstruction.

The emergence of multidrug-resistant Pseudomonas aeruginosa in healthcare settings poses a tremendous challenge to traditional antibiotic therapy. Pseudomonas aeruginosa utilizes quorum sensing (QS) to coordinate the production of virulence factors and the formation of drug-resistant biofilms. QS is mediated by signal compounds produced by P. aeruginosa as well as signal molecules produced by other non-pseudomonad bacteria. A potential strategy to prevent bacterial pathogenicity is utilizing enzymes to interfere with QS. Here, we used AidC, a quorum-quenching (QQ) enzyme from Chryseobacterium sp. strain StRB126 that can effectively hydrolyze N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL) and N-butanoyl-homoserine lactone (C4-HSL), the major signal molecules synthesized by P. aeruginosa. The exogenous addition of AidC to P. aeruginosa wild-type strain PAO1 cultures significantly reduced the total protease and elastase activities and the production of pyocyanin. In addition, the application of AidC resulted in thin and sparse biofilm formation. Later, we used a metagenomic-derived QQ enzyme, QQ-2, in combination with AidC to attenuate PAO1 virulence when the presence of a non-pseudomonad signal compound, autoinducer-2, aggravated it. These findings suggest that using a combined antimicrobial approach may lead to a more efficacious therapeutic intervention against P. aeruginosa PAO1 infection, as its behavior is modulated in the presence of intraspecies and interspecies signal compounds.

One-sentence summary: In this work, the potential of dual enzymes was investigated to interfere with quorum sensing as a novel concept for reducing the virulence of P. aeruginosa, which is influenced by both intra species and interspecies communication.

Shewanella oneidensis MR-1 is an electroactive bacterium that is a promising host for bioelectrochemical technologies, which makes it a common target for genetic engineering, including gene deletions and expression of heterologous pathways. Expression of heterologous genes and gene knockdown via CRISPRi in S. oneidensis are both frequently induced by β-D-1-thiogalactopyranoside (IPTG), a commonly used inducer molecule across many model organisms. Here, we report and characterize an unexpected phenotype; IPTG enhances the growth of wild-type S. oneidensis MR-1 on the sugar substrate N-acetylglucosamine (NAG). IPTG improves the carrying capacity of S. oneidensis growing on NAG while the growth rate remains similar to cultures without the inducer. Extracellular acetate accumulates faster and to a higher concentration in cultures without IPTG than those with it. IPTG appears to improve acetate metabolism, which combats the negative effect that acetate accumulation has on the growth of S. oneidensis with NAG. We recommend using extensive experimental controls and careful data interpretation when using both NAG and IPTG in S. oneidensis cultures.

Eunicellane diterpenoids are a remarkable family of terpene natural products and have been of high interest for over five decades. Widely distributed in soft corals and rare in plants, eunicellanes were also recently identified in actinobacteria. These terpenoids have foundational 6/10-bicyclic frameworks that are frequently oxidized into structures containing transannular ether bridges. Interest in their unique structures and promising biological activities, such as the paclitaxel-like activities of eleutherobin and the sarcodictyins, has led to advancements in natural product isolation, total synthesis, medicinal chemistry, and drug lead development. Until recently, however, there was little known about the biosynthesis and enzymology of these natural products, but several recent studies in both bacteria and coral have opened up the field. This review summarizes recent advancements in the biosynthesis and enzymology of eunicellane diterpenoids and highlights future research prospects in the field.

One-sentence summary: A summary of recent advancements in the biosynthesis and enzymology of eunicellane diterpenoids, a structurally unique and biologically active family of natural products found in coral, plants, and bacteria.

Long-term storage is necessary to mitigate for seasonal variation in algae productivity, to preserve biomass quality and to guarantee a constant biomass supply to a conversion facility. While ensiling has shown promise as a solution, biomass attributes for successful storage are poorly understood. Storage studies of Monoraphidium sp. biomass indicate a strong correlation between nitrogen management in algae cultivation and stability of post-harvest algae biomass. Algae cultivated with periodic nitrogen addition were stored poorly (>20% loss, dry basis) compared to biomass from nitrogen depleted cultivation (8% loss, dry basis). A follow-up study compared the post-harvest stability of Monoraphidium biomass cultivated in nitrogen-deplete or nitrogen-replete conditions. Replete biomass experienced the largest degradation (24%, dry basis), while deplete biomass experienced the least (10%, dry basis). Dry matter loss experienced among blends of each correlated positively with nitrogen-replete biomass content. The composition of the post-storage algae microbial community was also affected by cultivation conditions, with Clostridia species being more prevalent in stored biomass obtained from nitrogen-replete cultivations. Nitrogen management has long been known to influence algae biomass productivity and biochemical composition; here, we demonstrate that it also strongly influences the stability of post-harvest algae biomass in anaerobic storage.

Natural products have found important applications in the pharmaceutical and agricultural sectors. In bacteria, the genes that encode the biosynthesis of natural products are often colocalized in the genome, forming biosynthetic gene clusters. It has been predicted that only 3% of natural products encoded in bacterial genomes have been discovered thus far, in part because gene clusters may be poorly expressed under laboratory conditions. Heterologous expression can help convert bioinformatics predictions into products. However, challenges remain, such as gene cluster prioritization, cloning of the complete gene cluster, high level expression, product identification, and isolation of products in practical yields. Here we reviewed the literature from the past 5 years (January 2018 to June 2023) to identify studies that discovered natural products by heterologous expression. From the 50 studies identified, we present analyses of the rationale for gene cluster prioritization, cloning methods, biosynthetic class, source taxa, and host choice. Combined, the 50 studies led to the discovery of 63 new families of natural products, supporting heterologous expression as a promising way to access novel chemistry. However, the success rate of natural product detection varied from 11% to 32% based on four large-scale studies that were part of the reviewed literature. The low success rate makes it apparent that much remains to be improved. The potential reasons for failure and points to be considered to improve the chances of success are discussed.

One-sentence summary: At least 63 new families of bacterial natural products were discovered using heterologous expression in the last 5 years, supporting heterologous expression as a promising way to access novel chemistry; however, the success rate is low (11-32%) making it apparent that much remains to be improved-we discuss the potential reasons for failure and points to be considered to improve the chances of success. BioRender was used to generate the graphical abstract figure.

Bacteria have long been a source of natural products with diverse bioactivities that have been developed into therapeutics to treat human disease. Historically, researchers have focused on a few taxa of bacteria, mainly Streptomyces and other actinomycetes. This strategy was initially highly successful and resulted in the golden era of antibiotic discovery. The golden era ended when the most common antibiotics from Streptomyces had been discovered. Rediscovery of known compounds has plagued natural product discovery ever since. Recently, there has been increasing interest in identifying other taxa that produce bioactive natural products. Several bioinformatics studies have identified promising taxa with high biosynthetic capacity. However, these studies do not address the question of whether any of the products produced by these taxa are likely to have activities that will make them useful as human therapeutics. We address this gap by applying a recently developed machine learning tool that predicts natural product activity from biosynthetic gene cluster (BGC) sequences to determine which taxa are likely to produce compounds that are not only novel but also bioactive. This machine learning tool is trained on a dataset of BGC-natural product activity pairs and relies on counts of different protein domains and resistance genes in the BGC to make its predictions. We find that rare and understudied actinomycetes are the most promising sources for novel active compounds. There are also several taxa outside of actinomycetes that are likely to produce novel active compounds. We also find that most strains of Streptomyces likely produce both characterized and uncharacterized bioactive natural products. The results of this study provide guidelines to increase the efficiency of future bioprospecting efforts.

One-sentence summary: This paper combines several bioinformatics workflows to identify which genera of bacteria are most likely to produce novel natural products with useful bioactivities such as antibacterial, antitumor, or antifungal activity.

Astaxanthin has high utilization value in functional food because of its strong antioxidant capacity. However, the astaxanthin content of Phaffia rhodozyma is relatively low. Adaptive laboratory evolution is an excellent method to obtain high-yield strains. TiO2 is a good inducer of oxidative stress. In this study, different concentrations of TiO2 were used to domesticate P. rhodozyma, and at a concentration of 1000 mg/L of TiO2 for 105 days, the optimal strain JMU-ALE105 for astaxanthin production was obtained. After fermentation, the astaxanthin content reached 6.50 mg/g, which was 41.61% higher than that of the original strain. The ALE105 strain was fermented by batch and fed-batch, and the astaxanthin content reached 6.81 mg/g. Transcriptomics analysis showed that the astaxanthin synthesis pathway, and fatty acid, pyruvate, and nitrogen metabolism pathway of the ALE105 strain were significantly upregulated. Based on the nitrogen metabolism pathway, the nitrogen source was adjusted by ammonium sulphate fed-batch fermentation, which increased the astaxanthin content, reaching 8.36 mg/g. This study provides a technical basis and theoretical research for promoting industrialization of astaxanthin production of P. rhodozyma.

One-sentence summary: A high-yield astaxanthin strain (ALE105) was obtained through TiO2 domestication, and its metabolic mechanism was analysed by transcriptomics, which combined with nitrogen source regulation to further improve astaxanthin yield.