Biology subjects

Li, S.

Publications and source records attributed to Li, S..

At least 991 records · Page 55Linked to original sources

bioRxiv2021

HIV-1 Nef and CycK:CDK13 antagonize SERINC5 for optimal viral infectivity

HIV-1 Nef antagonizes SERINC5 by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identified cyclin K and cyclin-dependent kinase 13 (CycK:CDK13) as a new Nef-associated kinase complex. CycK:CDK13 phosphorylates the serine at position 360 (S360) in SERINC5, which is required for Nef downregulation of SERINC5 from the cell surface and its counter activity of the SERINC5 antiviral activity. To understand the role of S360 phosphorylation, we created chimeric proteins between CD8 and SERINC5. Nef not only downregulates, but importantly, also binds to this chimera in a S360-dependent manner. Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.

microbiology↗

bioRxiv2021

Transient nuclear deformation primes epigenetic state and promotes cell reprogramming

Cell reprogramming has wide applications in tissue regeneration, disease modeling and personalized medicine, but low reprogramming efficiency remains a challenge. In addition to biochemical cues, biophysical factors can modulate the epigenetic state and a variety of cell functions. However, how biophysical factors help overcome the epigenetic barrier for cell reprogramming are not well understood. Here we utilized microfluidic channels to induce a transient deformation of the cell nucleus, which caused the disassembly of the nuclear lamina and a downregulation of DNA methylation and histone (H3K9) for 12-24 hours. These global decreases of heterochromatin marks at the early stage of cell reprogramming strikingly enhanced the conversion of fibroblasts into neurons and induced pluripotent stem cells. Consistently, inhibition of DNA methylation and H3K9 methylation partially mimicked the effects of mechanical squeezing on iN reprogramming efficiency. Knocking down lamin A had similar effects to squeezing on enhancing the reprogramming efficiency. Based on these findings, we developed a scalable microfluidic system that enabled a continuous cell processing to effectively prime the epigenetic state for cell reprogramming, demonstrating the potential of mechano-biotechnology for cell engineering.

biophysics↗

bioRxiv2021

A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis

Under stress, the endomembrane system undergoes reorganization to support autophagosome biogenesis, which is a central step in autophagy. How the endomembrane system remodels has been poorly understood. Here we identify a new type of membrane contact formed between the ER-Golgi intermediate compartment (ERGIC) and the ER-exit site (ERES) in the ER-Golgi system, which is essential for promoting autophagosome biogenesis induced by different stress stimuli. The ERGIC-ERES contact is established by the interaction between TMED9 and SEC12 which generates a short distance opposition (as close as 2-5 nm) between the two compartments. The tight membrane contact allows the ERES-located SEC12 to transactivate COPII assembly on the ERGIC. In addition, a portion of SEC12 also relocates to the ERGIC. Through both mechanisms, the ERGIC-ERES contact promotes formation of the ERGIC-derived COPII vesicle, a membrane precursor of the autophagosome. The ERGIC-ERES contact is physically and functionally different from the TFG-mediated ERGIC-ERES adjunction involved in secretory protein transport, and therefore defines a unique endomembrane structure generated upon stress conditions for autophagic membrane formation.

cell biology↗

bioRxiv2021

Mechanistic insights into dideoxygenation in gentamicin biosynthesis

Gentamicin is an important aminoglycoside antibiotic used for treatment of infections caused by Gram-negative bacteria. Although most of the biosynthetic pathway of gentamicin has been elucidated, a remaining intriguing question is how the intermediates JI-20A and JI-20B undergo a dideoxygenation to form gentamicin C complex. Here we show that the dideoxygenation process starts with GenP-catalyzed phosphorylation of JI-20A and JI-20Ba. The phosphorylated products are converted to C1a and C2a by concerted actions of two PLP (pyridoxal 5-phosphate)-dependent enzymes: elimination of water and then phosphate by GenB3 and double bond migration by GenB4. Each of these reactions liberates an imine which hydrolyses to a ketone or aldehyde and is then re-aminated by GenB3 using an amino donor. Crystal structures of GenB3 and GenB4 have guided site-directed mutagenesis to reveal crucial residues for the enzymes functions. We propose catalytic mechanisms for GenB3 and GenB4, which shed new light on the already unrivalled catalytic versatility of PLP-dependent enzymes.

microbiology↗

bioRxiv2021

Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability

Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA Polymerase II (Pol II), causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions (TBLs). However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR/cas9 screen, we identified elongation factor ELOF1 as an important new factor in the transcription stress response upon DNA damage. We show that ELOF1 has an evolutionary conserved role in Transcription-Coupled Nucleotide Excision Repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair TBLs and resume transcription. Additionally, ELOF1 modulates transcription to protect cells from transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage by two distinct mechanisms.

cell biology↗

bioRxiv2021

Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta

The majority of clinical deaths among patients with triple-negative breast cancer (TNBC) are caused by uncontrolled cell proliferation and aggressive metastases, which is regulated by hyperactive glycogen synthase kinase 3 beta (GSK3{beta}); however, the underlying mechanisms remain largely unknown. In the present study, we found that protein phosphatase 1 regulatory inhibitor subunit 14C (PPP1R14C) was specifically upregulated in TNBC, compared with that in normal tissues and non-TNBC. High PPP1R14C expression correlated significantly with shorter 5-year relapse-free survival and overall survival in patients with TNBC. Overexpressing PPP1R14C promoted, while suppression of PPP1R14C decreased the cell proliferation and the aggressive phenotype of TNBC cells, in vitro and in vivo. Importantly, we revealed that PPP1R14C interacted with and inactivated type 1 Ser/Thr protein phosphatase (PP1) to sustain GSK3{beta} phosphorylation at S9, and induced the ubiquitylation and degradation of non-phosphorylated GSK3{beta} (S9A) via recruiting E3 ligase, TRIM25. Furthermore, treating with C2 ceramide (C2), which recovered kinase activity of GSK3{beta}, resulted in tumor growth inhibition in PPP1R14C-overexpressing TNBC cells. Our findings reveal a novel mechanism whereby PPP1R14C sustains inactive GSK3{beta}, which might lead to targeted therapy for TNBC.

cancer biology↗

bioRxiv2021

AutoVEM2: a flexible automated tool to analyze candidate key mutations and epidemic trends for virus

In our previous work, we developed an automated tool, AutoVEM, for real-time monitoring the candidate key mutations and epidemic trends of SARS-CoV-2. In this research, we further developed AutoVEM into AutoVEM2. AutoVEM2 is composed of three modules, including call module, analysis module, and plot module, which can be used modularly or as a whole for any virus, as long as the corresponding reference genome is provided. Therefore, its much more flexible than AutoVEM. Here, we analyzed three existing viruses by AutoVEM2, including SARS-CoV-2, HBV and HPV-16, to show the functions, effectiveness and flexibility of AutoVEM2. We found that the N501Y locus was almost completely linked to the other 16 loci in SARS-CoV-2 genomes from the UK and Europe. Among the 17 loci, 5 loci were on the S protein and all of the five mutations cause amino acid changes, which may influence the epidemic traits of SARS-CoV-2. And some candidate key mutations of HBV and HPV-16, including T350G of HPV-16 and C659T of HBV, were detected. In brief, we developed a flexible automated tool to analyze candidate key mutations and epidemic trends for any virus, which would become a standard process for virus analysis based on genome sequences in the future. HighlightsO_LIAn automatic tool to quickly analyze candidate key mutations and epidemic trends for any virus was developed. C_LIO_LIOur integrated analysis method and tool could become a standard process for virus mutation and epidemic trend analysis based on genome sequences in the future. C_LIO_LIN501Y with the other 16 highly linked mutation sites of SARS-CoV-2 in the UK and Europe were further confirmed, and some valuable mutation sites of HBV and HPV-16 were detected. C_LI

genomics↗

bioRxiv2021

DNA methylation calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation

BackgroundNanopore long-read sequencing technology greatly expands the capacity of long-range single-molecule DNA-modification detection. A growing number of analytical tools have been actively developed to detect DNA methylation from Nanopore sequencing reads. Here, we examine the performance of different methylation calling tools to provide a systematic evaluation to guide practitioners for human epigenome-wide research. ResultsWe compare five analytic frameworks for detecting DNA modification from Nanopore long-read sequencing data. We evaluate the association between genomic context, CpG methylation-detection accuracy, CpG sites coverage, and running time using Nanopore sequencing data from natural human DNA. Furthermore, we provide an online DNA methylation database (https://nanome.jax.org) with which to display genomic regions that exhibit differences in DNA-modification detection power among different methylation calling algorithms for nanopore sequencing data. ConclusionsOur study is the first benchmark of computational methods for mammalian whole genome DNA-modification detection in Nanopore sequencing. We provide a broad foundation for cross-platform standardization, and an evaluation of analytical tools designed for genome-scale modified-base detection using Nanopore sequencing.

bioinformatics↗

bioRxiv2021

Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of SARS-CoV-2 infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identified 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, ACE2-blocking clone that protects in vivo), and others recognizing non-RBD epitopes that bound the heptad repeat 1 region of the S2 domain. Germline-revertant forms of some public clonotypes bound efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

immunology↗

bioRxiv2021

Multi-tissue integrative analysis of personal epigenomes

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of personal epigenomes, for [~]25 tissues and >10 assays in four donors (>1500 open-access functional genomic and proteomic datasets, in total). Each dataset is mapped to a matched, diploid personal genome, which has long-read phasing and structural variants. The mappings enable us to identify >1 million loci with allele-specific behavior. These loci exhibit coordinated epigenetic activity along haplotypes and less conservation than matched, non-allele-specific loci, in a fashion broadly paralleling tissue-specificity. Surprisingly, they can be accurately modelled just based on local nucleotide-sequence context. Combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci and enables models for transferring known eQTLs to difficult-to-profile tissues. Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

genomics↗

bioRxiv2021

METTL9 regulates N1-histidine methylation of zinc transporters to promote tumor growth

Methyltransferase like 9 (Mettl9) is a member of the methyltransferase like protein family which is characterized by the presence of binding domains for S-adenosyl methionine, (SAM), a co-substrate for methylation reactions. Despite METTL9 is predicted to be a methyltransferase, its enzymatic activity, substrate specificities and biological functions are still poorly characterized. In this study, we revealed a tumor-promoting role for METTL9. We found that deletion of Mettl9 in tumor cells suppresses tumor growth and elicits potent anti-tumor immunity. Mechanistically, METTL9 is a N1-histidine methyltransferase which methylates the histidine residues of a x-His-x-His (xHxH) motif on the substrates. This motif is found extensively in zinc transporter families SLC39s and SLC30s, particularly in SLC39A7. Deletion of Mettl9 impairs cytoplasmic zinc homeostasis, resulting in an altered gene expression program with increased endoplasmic reticulum (ER) stress and reduced cell cycle. Mutation of key METTL9 catalyzed methylhistidine residues of SLC39A7 impairs cytoplasmic zinc homeostasis and affects cell growth as well. Notably, METTL9 expression is increased in some cancer types and its higher expression is associated with worse clinical outcomes, particularly in liver and pancreatic cancer. In summary, our work identified METTL9 as a potential new oncogene and its mediated methylation is of regulatory importance. Identifying selective and potent small-molecule inhibitors of METTL9 could thus represent novel therapeutic strategy for anti-proliferative cancer drugs.

cancer biology↗

bioRxiv2021

Three bacterium-plasmid golden combinations facilitate the spread of ST11/CG258 carbapenemase-producing Klebsiella pneumoniae in China

Carbapenemase-producing Klebsiella pneumoniae (cpKP) poses serious threats to public health. Previous studies showed that only ST11/CG258-cpKP successfully disseminated in China, however, the underlying genetic bases are still unknown. We conducted a comprehensive genomic-epidemiology analysis on 420 cpKP isolates from 70 hospitals in 24 Chinese provinces during 2009-2017 based on short-/long-reads sequencing. Three golden combinations of host--blaKPC-carrying plasmids (Clade 3.1+3.2--IncFIIpHN7A8, Clade 3.1+3.2--IncFIIpHN7A8:IncR, Clade 3.3--IncFIIpHN7A8:IncpA1763-KPC) endowed cpKP with advantages both in genotypes (strong-correlation/co-evolution) and phenotypes (resistance/growth/competition), thereby facilitating nationwide spread of ST11/CG258-cpKP. Intriguingly, Bayesian skyline illustrated that the three golden combinations might directly lead to the strong population expansion during 2007-2008 and subsequent maintenance of the dissemination of ST11/CG258-cpKP after 2008. We tested drug-resistance profiles and proposed combination treatment regimens for CG258/non-CG258 cpKP. Our findings systematically revealed the molecular-epidemiology and genetic-basis for dissemination of Chinese ST11/CG258 cpKP and reminded us to monitor the golden combinations of cpKP- plasmid closely.

microbiology↗

bioRxiv2021

Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus displayed remarkable efficacy against authentic B.1.351 virus. Each of these 3 mAbs in combination with one neutralizing Ab recognizing non-competing epitope exhibited synergistic effect against authentic SARS-CoV-2 virus. Surprisingly, structural analysis revealed that 58G6 and 13G9, encoded by the IGHV1-58 and the IGKV3-20 germline genes, both recognized the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly bound to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrated prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. These 2 ultrapotent neutralizing Abs can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.

immunology↗

bioRxiv2021

Genetic diversity, evolutionary dynamics and pathogenicity of ferret badger rabies virus variants in mainland China, 2008-2018

In contrast to dog associated human rabies cases decline year by year due to the rabies vaccination coverage rates increase in China, ferret badger (FB, Melogale moschata)-associated human rabies cases emerged in the 1990s, and are now an increasingly recognized problem in southeast China. To investigate epidemiology, temporal evolution dynamics, transmission characterization and pathogenicity of FB-associated rabies viruses (RABVs), from 2008 to 2018, we collected 3,622 FB brain samples in Jiangxi and Zhejiang Province, and detected 112 RABV isolates. Four FB-related lineages were identified by phylogenetic analysis (lineages A-D), the estimated Times to Most Recent Common Ancestor were 1941, 1990, 1937 and 1997 for lineages A-D respectively. Furthermore, although no FB-associated human rabies case has been reported there apart from Wuyuan area, FB-RABV isolates are mainly distributed in Jiangxi Province. Pathogenicity of FB-RABVs was assessed using peripheral inoculation in mice and in beagles with masseter muscles, mortality-rates ranging from 20% to 100% in mice and 0 to 20% in beagles in the groups infected with the various isolates. Screening of sera from humans with FB bites and no postexposure prophylaxis to rabies, revealed that 5 of 9 were positive for neutralizing antibodies of RABV. All the results above indicated that FB-RABV variants caused a lesser pathogenicity in mice, beagles and even humans. Vaccination in mice suggests that inactivated vaccine or recombinant subunit vaccine products can be used to control FB- associated rabies, however, oral vaccines for stray dogs and wildlife need to be developed and licensed in China urgently. IMPORTANCEIn recent years FB-associated rabies virus has been identified as a major life-threatening pathogen in some districts in China. To understand the risk to public health and the contemporary dynamics, the present study conducted extensive investigations on FB rabies, distribution, virus isolation, phylogeny analysis, pathogenicity determination of various FB rabies virus strains, besides, serologic epidemiology survey to those whom bit by FB was also collected. The results show that the majority of FBs dwell in southeast China, like Jiangxi and Zhejiang Province, Phylogenetic analysis indicates that all isolated FB RABVs evolved from dogs, and the FB RABV can separate into 4 distinct lineages distributed relatively independent in different areas. The isolate strains differ in pathogenicity, although they have relatively lower pathogenicity compared to dog rabies virus according to our study, the need for further study to licensed oral vaccines and FB RABV pathogenesis is emphasized in order to control rabies.

pathology↗

bioRxiv2021

Anaerobic growth of Listeria monocytogenes on rhamnose is stimulated by Vitamin B12 and bacterial microcompartment dependent 1,2-propanediol utilization

The food-borne pathogen Listeria monocytogenes is able to form proteinaceous organelles called bacterial microcompartments (BMCs) that optimize the utilization of substrates, such as 1,2-propanediol, and confer an anaerobic growth advantage. Rhamnose is a deoxyhexose sugar abundant in a range of environments including the human intestine, and can be degraded in anaerobic conditions into 1,2-propanediol, next to acetate and lactate. Rhamnose-derived 1,2-propanediol has been found to link with BMCs in a limited number of commensal human colonic species and some human pathogens such as Salmonella enterica, but the involvement of BMCs in rhamnose metabolism and potential physiological effects on L. monocytogenes are still unknown. In this study, we firstly test the effect of rhamnose uptake and utilization on anaerobic growth of L. monocytogenes EGDe without and with added vitamin B12, followed by metabolic analysis. We unveil that the vitamin B12-dependent activation of pdu stimulates metabolism and anaerobic growth of L. monocytogenes EGDe on rhamnose via 1,2-propanediol degradation into 1-propanol and propionate. Transmission electron microscopy of pdu-induced cells shows that BMCs are formed and additional proteomics experiments confirm expression of pdu BMC shell proteins and enzymes. Finally, we discuss physiological effects and energy efficiency of L. monocytogenes pdu BMC-driven anaerobic rhamnose metabolism and impact on competitive fitness in environments such as the human intestine.

microbiology↗

bioRxiv2021

Perfecting and extending the near-infrared biological window

In vivo fluorescence imaging in the second near-infrared window (NIR-II) has been considered as a promising technique for visualizing the mammals. However, the definition of the NIR-II region and the mechanism accounting for the excellent performance still need to be perfected. Herein, we simulated bioimaging in the NIR spectral range (to 2340 nm), confirmed the positive contribution of moderate light absorption by water in intravital imaging and perfected the NIR-II window as 900-1880 nm, where the 1400-1500 nm was defined as NIR-IIx region and the 1700-1880 nm was defined as NIR-IIc region, respectively. Moreover, the 2080-2340 nm was newly proposed as the third near-infrared (NIR-III) window, which was believed to provide the best imaging quality. The wide-field fluorescence microscopy in brain, in addition, was performed around NIR-IIx region with excellent optical sectioning strength and the largest imaging depth of in vivo NIR-II fluorescence microscopy to date. We also proposed 1400 nm long-pass detection in off-peak NIR-II imaging whose profits exceeded those of NIR-IIb imaging, using bright fluorophores with short peak emission wavelength.

bioengineering↗

bioRxiv2021

Interaction of the Causal Agent of Apricot bud gall Acalitus phloeocoptes (Nalepa) with Apricot: Implications in Infested Tissues

Apricot bud gall mite, Acalitus phloeocoptes (Nalepa), is a destructive arthropod pest that causes significant economic losses to apricot trees worldwide. Infested bud examination revealed that the starch granules in the bud axon were extended at the onset of the attack. During the later stages of the attack, the cytoplasm was distributed in apricot. The results also demonstrated that the accumulation of large amounts of cytokinin (zeatin, ZT) and auxin (indoleacetic acid, IAA) led to rapid bud proliferation during the rapid growth period. Abscisic acid (ABA) controls the development of gall buds and plays a vital role in gall bud maturity. The reduction of gibberellic acid (GA3) content led to rapid lignification at the later phase of bud development. Our results reveal the mechanism underlying the interaction of apricot bud gall with its parasite and provide reliable information for designing valuable breeding programs. This study will be quite useful for pest management and will provide a comprehensive evaluation of ecology-based cost-effective control, life history and demographic parameters of A. phloeocoptes.

microbiology↗

bioRxiv2021

An inventory of early branch points in microbial phosphonate biosynthesis

Microbial phosphonate biosynthetic machinery has been identified in ~5% of bacterial genomes and encodes natural products like fosfomycin as well as cell surface decorations. Almost all biological phosphonates originate from the rearrangement of phosphoenolpyruvate (PEP) to phosphonopyruvate (PnPy) catalyzed by PEP mutase (Ppm), and PnPy is often converted to phosphonoacetaldehyde (PnAA) by PnPy decarboxylase (Ppd). Seven enzymes are known or likely to act on either PnPy or PnAA as early branch points en route to diverse biosynthetic outcomes, and these enzymes may be broadly classified into three reaction types: hydride transfer, aminotransfer, and carbon-carbon bond formation. However, the relative abundance of these branch points in microbial phosphonate biosynthesis is unknown. Also unknown is the proportion of ppm-containing gene neighborhoods encoding new branch point enzymes and potentially novel phosphonates. In this study we computationally sorted 434 ppm-containing gene neighborhoods based on these seven branch point enzymes. Unsurprisingly, the majority (56%) of these pathways encode for production of the common naturally occurring compound 2-aminoethylphosphonate (AEP) or a hydroxylated derivative. The next most abundant genetically encoded intermediates were phosphonoalanine (PnAla, 9.2%), 2-hydroxyethylphosphonate (HEP, 8.5%), and phosphonoacetate (PnAc, 6%). Significantly, about 13% of the gene neighborhoods could not be assigned to any of the seven branch points and may encode novel phosphonates. Sequence similarity network analysis revealed families of unusual gene neighborhoods including possible production of phosphonoacrylate and phosphonofructose, the apparent biosynthetic use of the C-P lyase operon, and a virus-encoded phosphonate. Overall, these results highlight the utility of branch point inventories to identify novel gene neighborhoods and guide future phosphonate discovery efforts. IMPACT STATEMENTMicrobially-produced phosphonates are relatively rare and underexplored but include medically and agriculturally important molecules like fosfomycin and phosphinothricin, respectively. Because a single enzyme called phosphoenolpyruvate mutase (Ppm) inititates almost all phosphonate production, the composition of the gene neighborhood surrounding a Ppm-encoding gene can inform hypotheses regarding the chemical output of this chromosomal region. After the initial Ppm-catalyzed reaction there are only a limited set of subsequently acting enzymes, or branch points, to direct these early-stage phosphonates to alternate chemical fates. However, the relative abundance of different branch points - or the existence of new ones - has not been evaluated. This study provides just such a branch point inventory to determine relative proportions of known branch points and assess the diversity within each branch point. Significantly, this study suggests that a significant proportion (~13%) of gene neighborhoods do not fit into known branch points and therefore may be fertile hunting grounds for new phosphonate biochemistry. Data SummarySupporting information is available at Scholars Portal Dataverse (https://dataverse.scholarsportal.info/) with DOI 10.5683/SP2/T33ZP6. This includes scripts and the network data for visualizing in BiG-SCAPE and Cytoscape.

biochemistry↗