RESUMO
Lectins are proteins that bind specifically and reversibly to carbohydrates, and some of them have significant anti-tumor activities. Compared to those of lectins from land plants, there are far fewer studies on algal lectins, despite of the high biodiversity of algae. However, canonical strategies based on chromatographic feature-oriented screening cannot satisfy the requirement for algal lectin discovery. In this study, prospecting for novel OAAH family lectins throughout 358 genomes of red algae and cyanobacteria was conducted. Then 35 candidate lectins and 1843 of their simulated mutated forms were virtually screened based on predicted binding specificities to characteristic carbohydrates on cancer cells inferred by a deep learning model. A new lectin, named Siye, was discovered in Kappaphycus alvarezii genome and further verified on different cancer cells. Without causing agglutination of erythrocytes, Siye showed significant cytotoxicity to four human cancer cell lines (IC50 values ranging from 0.11 to 3.95 µg/mL), including breast adenocarcinoma HCC1937, lung carcinoma A549, liver cancer HepG2 and romyelocytic leukemia HL60. And the cytotoxicity was induced through promoting apoptosis by regulating the caspase and the p53 pathway within 24 h. This study testifies the feasibility and efficiency of the genome mining guided by evolutionary theory and artificial intelligence in the discovery of algal lectins.
Assuntos
Antineoplásicos , Simulação por Computador , Rodófitas , Humanos , Rodófitas/química , Rodófitas/genética , Antineoplásicos/farmacologia , Antineoplásicos/química , Lectinas/farmacologia , Lectinas/química , Lectinas/genética , Lectinas/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Genoma , Algas ComestíveisRESUMO
Lectins are glycoproteins that can bind to specific carbohydrates, and different lectin families exhibit different biological activities. They are also present in the cyanobacteria and many of them have shown excellent therapeutic effect, which deserve for bioprospecting. However, in comparison to those from terrestrial plants, the current knowledge on cyanobacterial lectins is very limited. To this end, genome-wide analyses were performed to find out their evolutionary mode and motif patterns in 316 genomes of representative taxa. In results, 196 putative cyanobacterial lectins were dig out and 105 of them were classified into known families. Seven lectins were found to be belonged to distinct two lectin families, and they may have the potential activities of both lectin families. Whereas no MFP-2, Chitin, and Nictaba family lectins were found. What's more, the Legume lectin-like lectin family was found to be the richest and most complex in cyanobacteria, which could be a main research direction for future cyanobacterial lectin bioprospecting and development. Our classification and prediction of cyanobacteria lectins is expected to provide assistance in the development of lectin-based medicine and provide solutions to the current thorny viral and tumor diseases in humans.
Assuntos
Cianobactérias , Lectinas , Humanos , Lectinas/genética , Estudo de Associação Genômica Ampla , Cianobactérias/genética , Cianobactérias/metabolismo , Evolução Biológica , Glicoproteínas , Lectinas de Plantas/genéticaRESUMO
Cyanobacteria can acclimate to changing copper and iron concentrations in the environment via metal homeostasis, but a general mechanism for interpreting their dynamic relationships is sparse. In this study, we assessed growth and chlorophyll fluorescence of Synechocystis sp. PCC 6803 and investigated proteomic responses to copper and iron deductions. Results showed that copper and iron exerted reciprocal effect on the growth and photosynthesis of Synechocystis sp. PCC 6803 at combinations of different concentrations. And some proteins involved in the uptake of copper and iron and the photosynthetic electron transport system exhibit Cu-Fe proteomic association. The protein abundance under copper and iron deduction affected the photosynthetic electronic activity of Synechocystis sp. PCC 6803 and eventually affected the growth and photosynthesis. Based on these results, we hypothesize that the Cu-Fe proteomic association of Synechocystis sp. PCC 6803 can be elucidated via the uptake system of outer membrane-periplasmic space-inner plasma membrane-thylakoid membrane, and this association is mainly required to maintain electron transfer. This study provides a broader view regarding the proteomic association between Cu and Fe in cyanobacteria, which will shed light on the role of these two metal elements in cyanobacterial energy metabolism and biomass accumulation.
RESUMO
The eutrophic Bohai Sea receives large amount of suspended material, nutrients and contaminant from terrestrial runoff, and exchanges waters with the northern Yellow Sea through a narrow strait. This coastal region provides an ideal model system to study microbial biogeography. We performed high-throughput sequencing to investigate the distribution of bacterial taxa along spatial and environmental gradients. The results showed bacterial communities presented remarkable horizontal and vertical distribution under coastal gradients of spatial and environmental factors. Fourteen abundant taxa clustered the samples into three distinctive groups, reflecting typical habitats in shallow coastal water (seafloor depth ≤ 20 m), sunlit surface layer (at water surface with seafloor depth >20 m) and bottom water (at 2-3 m above sediment with seafloor depth >20 m). The most significant taxa of each cluster were determined by the least discriminant analysis effect size, and strongly correlated with spatial and environmental variables. Environmental factors (especially turbidity and nitrite) exhibited significant influences on bacterial beta-diversity in surface water (at 0 m sampling depth), while community similarity in bottom water (at 2-3 m above sediment) was mainly determined by depth. In both surface and bottom water, we found bacterial community similarity and the number of OTUs shared between every two sites decreased with increasing geographic distance. Bacterial dispersal was also affected by phosphate, which was possible due to the high ratios of IN/IP in this coastal sea area.
RESUMO
The Laizhou Bay is famous for aquaculture, but has been subject to eutrophication and contamination for years. High concentrations of nutrients from the Xiaoqing River are considered as the main cause for significant eutrophication in the west of Laizhou Bay. Here we present results of the research on sedimentary microbial assemblages along this spatial gradient between riverine and marine environments by high-throughput sequencing. The predominant phyla/classes of bacteria and fungi clustered the samples into two distinct provinces, while discriminant taxa of each province were strongly associated with spatial factors and inorganic nitrogen. Spatial variation of bacterial communities was mainly related with the distribution of phosphates, suggesting a phosphate-limitation pattern for the bacterial communities. Alpha- and beta-diversity of fungal communities exhibited a significant correlation with water depth. We consider the distinct distributional gradients of bacterial and fungal communities partly explain the different roles in the biogeochemical processes of coastal sediment.
Assuntos
Bactérias , Eutrofização , Sedimentos Geológicos/química , Aquicultura , Baías , Monitoramento Ambiental , Nitrogênio , RiosRESUMO
Phycobilisome is the major light-harvesting complex in cyanobacteria and red alga. It consists of phycobiliproteins and their associated linker peptides which play key role in absorption and unidirectional transfer of light energy and the stability of the whole complex system, respectively. Former researches on the evolution among PBPs and linker peptides had mainly focused on the phylogenetic analysis and selective evolution. Coevolution is the change that the conformation of one residue is interrupted by mutation and a compensatory change selected for in its interacting partner. Here, coevolutionary analysis of allophycocyanin, phycocyanin, and phycoerythrin and covariation analysis of linker peptides were performed. Coevolution analyses reveal that these sites are significantly correlated, showing strong evidence of the functional and structural importance of interactions among these residues. According to interprotein coevolution analysis, less interaction was found between PBPs and linker peptides. Our results also revealed the correlations between the coevolution and adaptive selection in PBS were not directly related, but probably demonstrated by the sites coupled under physical-chemical interactions.