Last update 19 Sep 2024

PHB

Last update 19 Sep 2024

Basic Info

Synonyms

PHB, PHB1, Prohibitin

+ [1]

Introduction

Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus (PubMed:11302691, PubMed:20959514, PubMed:28017329, PubMed:31522117). Plays a role in adipose tissue and glucose homeostasis in a sex-specific manner (By similarity). Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells (By similarity). In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (By similarity). Regulates mitochondrial respiration activity playing a role in cellular aging (PubMed:11302691). The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117). In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates (By similarity). Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity). In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses (PubMed:14500729). Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells (PubMed:31899195).

Drugs associated with PHB

KBB-NX derivatives(KBlueBio)

Target

PHB

Mechanism

PHB modulators

Active Org.

Chonnam National University [+1]

Originator Org.

Chonnam National University [+1]

Active Indication

Multiple Myeloma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Prohibitin targeting peptide 1

Target

PHB

Mechanism

PHB modulators [+1]

Active Org.-

Originator Org.

The University of Texas MD Anderson Cancer Center

Active Indication-

Inactive Indication

Obesity [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with PHB

NCT01262664 / TerminatedPhase 1IIT

A First-in-Man, Phase I Evaluation of A Single Cycle of Prohibitin Targeting Peptide 1 in Patients With Metastatic Prostate Cancer and Obesity

The goal of this clinical research study is to find the highest tolerable dose of PROHIBITIN-TP01 that can be given to patients with advanced prostate cancer for which there are no standard therapy options. The safety of this drug will also be studied.

Start Date24 May 2012

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with PHB

100 Translational Medicine associated with PHB

0 Patents (Medical) associated with PHB

2,736

Literatures (Medical) associated with PHB

01 Dec 2024·Applied Microbiology and Biotechnology

Metabolic modeling of Halomonas campaniensis improves polyhydroxybutyrate production under nitrogen limitation

Article

Author: Saa, Pedro A ; Licona-Cassani, Cuauhtemoc ; Mendoza, Sebastián N ; Deantas-Jahn, Carolina ; Orellana, Camila

AbstractPoly-hydroxybutyrate (PHB) is an environmentally friendly alternative for conventional fossil fuel-based plastics that is produced by various microorganisms. Large-scale PHB production is challenging due to the comparatively higher biomanufacturing costs. A PHB overproducer is the haloalkaliphilic bacterium Halomonas campaniensis, which has low nutritional requirements and can grow in cultures with high salt concentrations, rendering it resistant to contamination. Despite its virtues, the metabolic capabilities of H. campaniensis as well as the limitations hindering higher PHB production remain poorly studied. To address this limitation, we present HaloGEM, the first high-quality genome-scale metabolic network reconstruction, which encompasses 888 genes, 1528 reactions (1257 gene-associated), and 1274 metabolites. HaloGEM not only displays excellent agreement with previous growth data and experiments from this study, but it also revealed nitrogen as a limiting nutrient when growing aerobically under high salt concentrations using glucose as carbon source. Among different nitrogen source mixtures for optimal growth, HaloGEM predicted glutamate and arginine as a promising mixture producing increases of 54.2% and 153.4% in the biomass yield and PHB titer, respectively. Furthermore, the model was used to predict genetic interventions for increasing PHB yield, which were consistent with the rationale of previously reported strategies. Overall, the presented reconstruction advances our understanding of the metabolic capabilities of H. campaniensis for rationally engineering this next-generation industrial biotechnology platform.Key points

A comprehensive genome-scale metabolic reconstruction of H. campaniensis was developed.

Experiments and simulations predict N limitation in minimal media under aerobiosis.

In silico media design increased experimental biomass yield and PHB titer.

01 Dec 2024·MethodsX

CRISPR-editing of the virus vector Aedes albopictus cell line C6/36, illustrated by prohibitin 2 gene knockout

Article

Author: Chan, Shiu-Wan

Aedes mosquitoes are important virus vectors. We provide a toolkit for CRISPR-Cas9-editing of difficult-to-knockdown gene previously shown to be refractory to siRNA silencing in mosquito cells, which is pivotal in understanding vector biology, vector competence, host-pathogen interactions and in gene annotations. Starting from database searches of Ae. albopictus and the C6/36 cell line whole genome shotgun sequences for the prohibitin 2 (PHB2) gene, primers were designed to confirm the gene sequence in our laboratory-passaged C6/36 cell line for the correct design and cloning of CRISPR RNA into an insect plasmid vector to create a single guide RNA for the PHB2 gene target. After transfection of this plasmid vector into the C6/36 cells, cell clones selected by puromycin and/or limiting dilution were analyzed for insertions and deletions (INDELs) using PCR, sequencing and computational sequence decomposition. From this, we have identified mono-allelic and bi-allelic knockout cell clones. Using a mono-allelic knockout cell clone as an example, we characterized its INDELs by molecular cloning and computational analysis. Importantly, mono-allelic knockout was sufficient to reduce >80 % of PHB2 expression, which led to phenotypic switching and the propensity to form foci but was insufficient to affect growth rate or to inhibit Zika virus infection.•We provide a toolkit for CRISPR-Cas9-editing of the virus vector, Aedes albopictus C6/36 cell line•We validate this using a difficult-to-knockdown gene prohibitin 2•This toolkit is pivotal in understanding vector biology, vector competence, host-pathogen interactions and in gene annotations.

01 Dec 2024·Applied Microbiology and Biotechnology

Metabolic response to a heterologous poly-3-hydroxybutyrate (PHB) pathway in Phaeodactylum tricornutum

Article

Author: Signal, Brandon ; Windhagauer, Matthias ; Fabris, Michele ; Doblin, Martina A ; Kuzhiumparambil, Unnikrishnan ; Abbriano, Raffaela M

The marine diatom Phaeodactylum tricornutum is an emerging host for metabolic engineering, but little is known about how introduced pathways are integrated into the existing metabolic framework of the host or influence transgene expression. In this study, we expressed the heterologous poly-3-hydroxybutyrate (PHB) pathway using episomal expression, which draws on the precursor acetyl coenzyme-A (AcCoA). By experimentally perturbing cultivation conditions, we gained insight into the regulation of the endogenous metabolism in transgenic lines under various environmental scenarios, as well as on alterations in AcCoA flux within the host cell. Biosynthesis of PHB led to distinct shifts in the metabolome of the host, and further analysis revealed a condition-dependent relationship between endogenous and transgenic metabolic pathways. Under N limitation, which induced a significant increase in neutral lipid content, both metabolic and transcriptomic data suggest that AcCoA was preferably shunted into the endogenous pathway for lipid biosynthesis over the transgenic PHB pathway. In contrast, supply of organic carbon in the form of glycerol supported both fatty acid and PHB biosynthesis, suggesting cross-talk between cytosolic and plastidial AcCoA precursors. This is the first study to investigate the transcriptomic and metabolomic response of diatom cell lines expressing a heterologous multi-gene pathway under different environmental conditions, providing useful insights for future engineering attempts for pathways based on the precursor AcCoA. KEY POINTS: • PHB expression had minimal effects on transcription of adjacent pathways. • N limitation favoured native lipid rather than transgenic PHB synthesis. • Glycerol addition allowed simultaneous lipid and PHB accumulation.

News (Medical) associated with PHB

15 Sep 2022

·www.biospace.com

Yield10 Bioscience Chief Science Officer Dr. Kristi Snell to Present on Advancements in Producing PHA Bioplastic in Camelina at the ISBP 2022 Conference

WOBURN, Mass., Sept. 15, 2022 (GLOBE NEWSWIRE) -- Yield10 Bioscience, Inc., (Nasdaq:YTEN) (“Yield10” or the “Company”), an agricultural bioscience company, today announced that its Chief Science Officer Dr. Kristi Snell will present during the International Symposium on Biopolymers (“ISBP”) 2022 Conference. The event is taking place September 12 through September 16, 2022 in Sion, Switzerland. Dr. Snell will make a presentation on Friday, September 16, during the session entitled “Industrial Feedstocks and Polymer Production” scheduled for 9:20 am to 11:00 am local time (3:20 am to 5:00 am ET). Her presentation entitled “Breakthroughs in Plant Based Polyhydroxybutyrate (PHB) Production” will describe the successful engineering of a bacterial pathway for producing PHB in the cytosol of Camelina seed. Yield10 researchers are conducting a program intended to produce sustainable, low-cost PHA bioplastic materials in the seed of the Camelina plant. In a patent application filed in 2019, Yield10 described a new technology solution for deploying the PHB pathway in Camelina. Using this approach, Yield10 obtained Camelina plants showing up to 10.2 percent PHB in seed that had good emergence and survival in growth chambers. Subsequent field tests with prototype Camelina PHB containing lines have shown approximately six percent PHB in the seed in two consecutive years. In 2022, Yield10 planted PHB producing Camelina at acre-scale and has harvested the plants for PHB extraction, product prototyping, sampling and other business development activities. The development of elite PHA Camelina lines with yields in the 10 to 20 percent range is ongoing, as well as the engineering of PHA copolymers in Camelina. “We have successfully demonstrated proof of concept for producing PHA bioplastics in Camelina seed by leveraging advanced tools in synthetic biology,” said Kristi Snell, Ph.D., Chief Science Officer of Yield10 Bioscience. “This spring we grew prototype PHA Camelina at acre-scale. We have now harvested the crop and plan to extract the PHA from seed for business development purposes. We have also engineered PHA production in winter Camelina lines which we plan to test for the first time in our 2022/2023 winter field trial program. As we move this program forward, we are pursuing multiple strategies to achieve our goal of reaching PHA yields of 10 to 20 percent in Camelina seed in field grown plants.” Learn more about the ISBP 2022 on the conference website. A copy of Dr. Snell’s slide deck is available on the Yield10 Bioscience investor relations website. Background on PHA Bioplastics Global plastic waste is estimated at 380 million metric tons per year. The largest market for plastics today is for packaging materials, and it accounts for nearly half of all plastic waste generated globally, where most of it is never recycled or incinerated. We believe there may be significant market opportunity for producing PHA biomaterials in Camelina in the future. PHA biomaterials (PHAs) are natural microbial high molecular weight polymeric storage polymers. These polymers are natural polyesters and can be recovered from the microbes that produce them and processed using standard plastics processing equipment into a range of product forms. The production of PHA bioplastics in Camelina could represent an entirely new market opportunity for farmers. This opportunity could provide economic returns for farmers to justify large acreage adoption of Camelina as a cover crop and enable the low-cost production of this product for new markets including water treatment and sustainable biodegradable plastics replacement applications. About Camelina sativa Camelina sativa, commonly known as Camelina or false flax, is an annual oilseed plant in the mustard family that is native to Europe. Camelina has the potential to replicate the development of modern canola from rapeseed on an accelerated timeline based on modern technologies, including genomics and genome editing. Additionally, Camelina grows on marginal lands, displays early maturation, has enhanced drought and cold tolerance, and requires fewer inputs than other oilseed crops. With social conscience and sustainability in mind, Yield10 is leveraging its innovations in Camelina to use it as a platform crop for producing low-carbon feedstock oil for renewable fuel; omega-3 nutritional oils; high-protein meal; and PHA bioplastic. AboutYield10 Bioscience Yield10 Bioscience, Inc. is an agricultural bioscience company that is using its differentiated trait gene discovery platform, the “Trait Factory”, to develop improved Camelina varieties for the production of proprietary seed products, and to discover high value genetic traits for the agriculture and food industries. Our goals are to efficiently establish a high value seed products business based on developing superior varieties of Camelina to produce biofuel feedstock oils, PHA bioplastics and omega-3 (DHA+EPA) oils and to license our yield traits to major seed companies for commercialization in major row crops, including corn, soybean and canola. Yield10 is headquartered in Woburn, MA and has an Oilseeds Center of Excellence in Saskatoon, Canada. For more information about the company, please visit , or follow the Company on Twitter, Facebook and LinkedIn. (YTEN-G) Safe Harbor forForward-LookingStatements This press release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements in this release do not constitute guarantees of future performance. Investors are cautioned that statements in this press release which are not strictly historical, including, without limitation, the Company’s plans with respect to Camelina business development and field testing; the Company’s goals relating to PHA yields in Camelina seed; and the Company’s beliefs about the market opportunity for PHA biomaterials and bioplastics, constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including the risks and uncertainties detailed in Yield10 Bioscience's filings with the Securities and Exchange Commission. Yield10 assumes no obligation to update any forward-looking information contained in this press release or with respect to the matters described herein. Contacts: Yield10 Bioscience: Lynne H. Brum, (617) 682-4693, LBrum@yield10bio.com Investor Relations: Bret Shapiro, (561) 479-8566, brets@coreir.com Managing Director, CORE IR Media Inquiries: Eric Fischgrund, eric@fischtankpr.com FischTank PR

CollaborateGene Therapy

15 Jun 2022

·www.globenewswire.com

Yield10 Bioscience Chief Science Officer Dr. Kristi Snell to Present on Advancements in Producing PHA Bioplastic in Camelina at the CROPS 2022: Improving Agriculture Through Genomics Conference

WOBURN, Mass., June 15, 2022 (GLOBE NEWSWIRE) -- Yield10 Bioscience, Inc. (Nasdaq:YTEN) (“Yield10” or the “Company”), an agricultural bioscience company, today announced that its Chief Science Officer Dr. Kristi Snell will present during the CROPS 2022: Improving Agriculture Through Genomics Conference taking place June 13 through June 16, 2022 in Huntsville, Alabama. Dr. Snell will make a presentation on Wednesday, June 15, during the session entitled “Plant Engineering for Increased Sustainability” scheduled for 9:10 am – 10:50 am CT (10:10 am – 11:50 am ET). Her presentation entitled “Breakthroughs in Plant Based Polyhydroxybutyrate (PHB) Production” will describe insights into the plant biology of Camelina that led to the successful engineering of a bacterial pathway for producing PHB in the cytosol of Camelina seed. Yield10 researchers have conducted a research program aimed at producing PHA bioplastics in the seed of the Camelina plant as a sustainable, low-cost method for producing this material. Yield10 developed a new technology solution for deploying the PHB pathway and filed a patent application in 2019. Using this approach, Yield10 obtained Camelina plants showing up to 10.2 percent PHB in seed that had good emergence and survival in growth chambers. Subsequent field tests with prototype Camelina PHB containing lines have shown approximately six percent PHB in the seed in two consecutive years. In 2022, Yield10 is planting at acre-scale the leading plant line in order to harvest PHB for product prototyping, sampling and other business development activities. The development of elite PHA Camelina lines with yields in the 10 to 20 percent range is ongoing as well as the engineering of PHA copolymers in Camelina. “Our team has leveraged advanced tools in synthetic biology to successfully demonstrate proof of concept for producing PHA bioplastics in Camelina seed,” said Kristi Snell, Ph.D., Chief Science Officer of Yield10 Bioscience. “This spring we are growing prototype PHA Camelina at the acre-scale and plan to extract the PHA from seed for business development use. We have also deployed PHA in winter Camelina lines and will test those for the first time in the field later this year. As we move the program ahead, we are pursuing multiple strategies to achieve our goal of reaching PHA yields of 10 to 20 percent in Camelina seed from field grown plants.” Learn more about the CROPS 2022: Improving Agriculture Through Genomics conference on the conference website. A copy of Dr. Snell’s slide deck is available on the Yield10 Bioscience investor relations website. Background on PHA Bioplastics Global plastic waste is estimated at 380 million metric tons per year. The largest market for plastics today is for packaging materials, and it accounts for nearly half of all plastic waste generated globally, where most of it is never recycled or incinerated. We believe there may be significant market opportunity for producing PHA biomaterials in Camelina in the future. PHA biomaterials (PHAs) are natural microbial high molecular weight polymeric storage polymers. These polymers are natural polyesters and can be recovered from the microbes that produce them and processed using standard plastics processing equipment into a range of product forms. The production of PHA bioplastics in Camelina could represent an entirely new market opportunity for farmers. This opportunity could provide economic returns for farmers to justify large acreage adoption of Camelina as a cover crop and enable the low-cost production of this product for new markets including water treatment and sustainable biodegradable plastics replacement applications. About Camelina sativa Camelina sativa, commonly known as Camelina or false flax, is an annual oilseed plant in the mustard family that is native to Europe. Camelina has the potential to replicate the development of modern canola from rapeseed on an accelerated timeline based on modern technologies, including genomics and genome editing. Additionally, Camelina grows on marginal lands, displays early maturation, has enhanced drought and cold tolerance, and requires fewer inputs than other oilseed crops. With social conscience and sustainability in mind, Yield10 is leveraging its innovations in Camelina to use it as a platform crop for producing low-carbon feedstock oil for renewable fuel; omega-3 nutritional oils; high-protein meal; and PHA bioplastic. About Yield10 Bioscience Yield10 Bioscience, Inc. is an agricultural bioscience company that is using its differentiated trait gene discovery platform, the “Trait Factory”, to develop improved Camelina varieties for the production of proprietary seed products, and to discover high value genetic traits for the agriculture and food industries. Our goals are to efficiently establish a high value seed products business based on developing superior varieties of Camelina to produce biofuel feedstock oils, PHA bioplastics and omega-3 (DHA+EPA) oils and to license our yield traits to major seed companies for commercialization in major row crops, including corn, soybean and canola. Yield10 is headquartered in Woburn, MA and has an Oilseeds Center of Excellence in Saskatoon, Canada. For more information about the company, please visit www.yield10bio.com, or follow the Company on Twitter, Facebook and LinkedIn. (YTEN-G) Safe Harbor for Forward-Looking Statements This press release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements in this release do not constitute guarantees of future performance. Investors are cautioned that statements in this press release which are not strictly historical, including, without limitation, the Company’s plans and expectations related to the development, engineering, growing and harvesting of Camelina, including PHA yield goals, and the Company’s expectations related to the economic opportunity of Camelina and PHA bioplastics, constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including the risks and uncertainties detailed in Yield10 Bioscience's filings with the Securities and Exchange Commission. Yield10 assumes no obligation to update any forward-looking information contained in this press release or with respect to the matters described herein. Contacts: Yield10 Bioscience:Lynne H. Brum, (617) 682-4693, LBrum@yield10bio.com Investor Relations: Bret Shapiro, (561) 479-8566, brets@coreir.comManaging Director, CORE IR Media Inquiries: Eric Fischgrund, eric@fischtankpr.com FischTank PR

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PHB

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