【Highlights】
►DNA Engineered protein with sequence response properties
► Synthetic translation regulation system based on RNA aptamer-protein binding and RNA origami scaffold
► Synthetic nerve fibers that enable parallel signal transmission
►MicroGEM's newly launched salivary COVID-19 detection method has received FDA emergency use authorization
►Ginkgo has reached a cooperation with Bayer to expand its agricultural biological products platform capabilities
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[Academic Information]
01 Cell Reports Methods
Engineered proteins with DNA sequence response characteristics (18 April 2022)
Nature has created the CRISPR-Cas system wonderfully, so can we use the idea of synthetic biology to imitate nature to build a protein activity switch with specific DNA sequence response characteristics? Recently, Sekhon and Loh from the Department of Biochemistry and Molecular Biology at SUNY Upstate Medical University published a research result in Cell Reports Methods, a new sub-journal of Cell. By fusing NanoLuc luciferase (nLuc), green fluorescent protein mutant mNeonGreen (mNG) and the double-stranded DNA binding domain of the yeast transcription factor GCN4, an efficient biosensor that responds to the GCN4 recognition sequence AP-1 was successfully constructed. On this basis, through different DNA sequence modification methods, biosensors that respond to serotonin, ATP, and even realize dual-input logic gates can be designed.
（https://www.sciencedirect.com/science/article/pii/S2667237522000601）
02 Metabolic Engineering
effectively regulates the biosynthesis of ovidomycin in Streptomyces through the synergistic effect of the butenolide signaling system and the biosynthetic gene cluster (19 April 2022)
The high incidence of tumors and other diseases and the frequency of drug resistance development, making the discovery of new drugs imminent. Genome sequencing shows that there are a large number of secondary metabolism gene clusters in Streptomyces, which provides a rich source for drug screening. Ovidomycin is an anthracycline compound that is considered a promising drug candidate due to its antitumor and antitumor activity against Gram-positive bacteria . Previous studies have elucidated the main biosynthetic gene cluster (BGC) of ovidomycin, and found that knocking out the global regulatory gene adpA (which together with sabP and sabD forms the sabAPD gene cluster) can activate Streptomyces chromogenes ( Expression of ovidamycin BGC in Streptomyces ansochromogenes. However, there are currently no reports related to increased production of ovidomycin.
Recently, the team of Dr. Zhang Jihui from Institute of Microbiology, Chinese Academy of Sciences studied the role of deletion of carbon source and SAB compound (a butenolide signaling molecule synthesized under the regulation of sabAPD gene cluster) in activating the silent ovidomycin synthesis gene. synergy in the cluster. In addition, in further research, the team also improved the production of ovidomycin by overexpressing the glycolytic gene involved in primary metabolism (providing precursors for ovidomycin synthesis). These findings promote the understanding of the correlation between the signal regulation system and the utilization of carbon source in Streptomyces, and also lay the foundation for the further development and application of ovidomycin.
(https://www.sciencedirect.com/science/article/abs/pii/S1096717622000611)
03 ACS SynBio
Optimization of plant heterologous carotene production strategy (19 April 2022)
Glucoraphanin is a special metabolite discovered from cruciferous plants , which can be degraded to generate sulforaphane , which is a multifunctional inducer that can induce the body to produce II Type detoxifying enzymes - glutathione transferase and quinone reductase, these enzymes can produce resistance to a variety of carcinogens, thus playing an anti-cancer effect. Previous studies have used plant and microbial systems for heterologous production of carotenoids, but the production efficiency was very limited, which suggests that there may be some auxiliary genes that play a role in carboside biosynthesis. Recently, Patrick M. Shih's team from University of California, Davis conducted a transient expression combination of previously screened co-expression genes and rationally selected carotene biosynthesis bypass genes in Nicotiana benthamiana. . This strategy alleviated the metabolic bottleneck and ultimately increased the production of carotene by 4.74 times. Overall, this study improves the heterologous biosynthesis efficiency of carotenoside and lays a foundation for the development of stable and high-yield heterologous plant transformants in the future.
(https://pubs.acs.org/doi/10.1021/acssynbio.2c00030)
04 ACS SynBio
Synthetic translation regulation system based on RNA aptamer-protein binding and RNA origami scaffold (19 April 2022)
Gene expression regulation is an important component in synthetic biology pathway design. However, tools to regulate gene expression at the translational level are still rarely reported. Recently, the team of Professor Ebbe S. Andersen from Aarhus University in Denmark developed an aptamer (aptamer, essentially two hairpin structures) based on MS2 and PP7 that can be used in E. coli and a coat protein ( Coat proteins (CP) expression control method at the translational level. The general principle is: the coat protein (MCP and PCP respectively) from MS2 or PP7 single-stranded RNA phage can achieve high specificity binding with the MS2 hairpin structure (MS2hp) or PP7 hairpin structure (PP7hp) respectively, thus Inhibits the translation process. RNA origami scaffolds containing up to four aptamers (MS2hp or PP7hp) can competitively bind to these coat proteins and alleviate this inhibitory effect.
In further experiments, the team demonstrated that the increase in reporter protein expression (i.e., the increase in the expression level of the target gene ) depends on the concentration and number of aptamers on the RNA origami scaffold. Using this system, the team also successfully achieved regulation of the expression levels of enzymes in the deoxyviolacein biosynthetic branch pathway.
(https://pubs.acs.org/doi/10.1021/acssynbio.1c00608)
05 Nature Chemistry
Synthetic nerve fibers that enable parallel transmission of signals (21 April 2022)
Bioelectronic devices that are soft and do not require connecting wires have great development prospects in medicine, robotics and chemical computing. Recently, Hagan Bayley's team from the University of Oxford in the UK developed a bionic synthetic neuron, which is composed entirely of soft and flexible biological materials and can quickly transmit electrochemical signals over a distance of several centimeters.
Similar to natural nerve cells, synthetic neurons can also release neurotransmitters from their terminals and initiate a series of downstream reactions. The main building blocks of synthetic neurons are nanoscale water droplets and hydrogel fibers connected by lipid bilayers. At the interface, transport is powered by light-driven proton pumps and mediated by ion-conducting protein pores. By bundling multiple neurons into a bundle, different signals can be transmitted in parallel.This research broadens ideas for the research and application of synthetic materials and lays the foundation for the development of next-generation implants, soft machines and computing devices.
（https://www.nature.com/articles/s41557-022-00916-1）
06 Nature Communications
Reengineering the regulatory components of the quorum sensing system to achieve control of multiple metabolic pathways (21 April 2022)
Quorum sensing (QS) is a ubiquitous intercellular communication mechanism that can be used to autonomously and dynamically control metabolism. flux. However, currently developed QS circuits are still incapable of complex regulation of multiple groups of genes or operons for metabolic engineering applications because the functions of the genetic components in the pathways are not fully understood. Recently, Yuan Qipeng's team from Beijing University of Chemical Technology developed a QS variant library with high dynamic range and low leakage by redesigning the quorum sensing components, and successfully applied it to salicylic acid in E. coli Diverse metabolic control of and coumarin- biosynthetic pathways. Overall, this work expands the toolbox for dynamic control of multiple metabolic fluxes in complex metabolic contexts and provides a paradigm for designing metabolic pathways to achieve high-level synthesis of target products.
(https://www.nature.com/articles/s41467-022-29933-x)
07 Fuel
Research progress in cyanobacterial metabolic engineering for biofuel production (23 April 2022)
In today's society, the burning of fossil fuels has caused a lot of pollution and carbon emissions. The use of sustainable biofuels as a substitute can effectively improve this situation. The most popular biofuel at present is bioethanol , but it also has shortcomings such as hygroscopicity and low energy content, which makes the development targets of biofuels gradually shift to higher alcohols , alkanes and others that are similar to gasoline and diesel. Molecules with similar properties. As a photoautotrophic microorganism, cyanobacteria can convert carbon dioxide and water into carbon-rich lipids (which can be used as a substrate for biodiesel production) under light conditions. This conversion process is extremely efficient, even higher than traditional oil crops, therefore cyanobacteria are considered a potential source of biofuel production.
In addition, the genetic background of cyanobacteria is now relatively clear, and a number of toolboxes for genetic manipulation of cyanobacteria have been developed, which makes the engineering transformation of cyanobacteria more convenient. Recently, Professor Chen Shaolin's team from Northwest A&F University published a review article in the journal Fuel, reviewing the latest progress in cyanobacterial metabolic engineering and synthetic biology methods. The range of products produced ranges from ethanol to biodiesel and terpenoids Many compounds of the terpene class.
(https://libyw.ucas.ac.cn/https/7myu6CroLAXMrp7uaqvXiuvMGPPiXePJGjDIkzo3jzQKJg/science/article/pii/S0016 236122009747)
[Industry Information]
01 Starburst, Axiom & Boryung
Starburst Aerospace launches the first annual "Space Cares" Challenge to promote cutting-edge research such as synthetic biology in space (18 April 2022)
Starburst Aerospace, a multinational aerospace investment institution and information company, recently announced that it will cooperate with space Infrastructure developer Axiom Space and pharmaceutical company Boryung have partnered to launch the first annual "Care in Space" (CIS) challenge. The competition will provide commercialization support for emerging technologies and solutions to use space as an innovative platform for the development of new healthcare technologies to optimize health monitoring, diagnosis and treatment during space travel.
（https://www.prnewswire.com/news-releases/boryung-axiom-space-and-starburst-aerospace-announce-first-annual-care-in-space-challenge-301526866.html）
02 New Culture
Bolt The former vice president of Threads joins New Culture to help develop its animal-free cheese products (18 April 2022)
Bolt Threads is a spider silk material manufacturer that is committed to using microorganisms to produce spider silk materials. Recently, the company’s former vice president, Dr. Josh Kittelson, announced that he has joined New Culture, an animal-free cheese production company, to advance the development of its animal-free cheese products.
Kittelson has over 15 years of experience in molecular biology and strain engineering, focusing on designing structural proteins and engineering microorganisms for new applications.
New Culture is committed to developing animal-free dairy products that are indistinguishable from traditional products in taste, texture, functionality and nutritional content. Due to the lack of casein , animal-free cheeses tend to have worse taste and nutrition than cheeses made from cow's milk. To overcome this shortcoming, New Culture engineered microorganisms to produce caseins (alpha-casein, kappa casein, and beta casein). Casein, water, vegetable fats, microorganisms and minerals are then mixed to make mozzarella cheese .
（https://www.prnewswire.com/news-releases/boryung-axiom-space-and-starburst-aerospace-announce-first-annual-care-in-space-challenge-301526866.html）
03 MoleculeMind
"Molecular Mind" completed tens of millions of dollars in angel round financing (18 April 2022)
AI protein design platform company "MoleculeMind" announced that the company has completed tens of millions of dollars in angel round financing, led by Sequoia China Investment, Baidu Venture Capital, Life Park Venture Capital Fund, Core Air Capital, Future Qichuang and other following investors. This round of financing will be used to further expand the team, continue the evolution of the AI protein platform, and commercialize scientific research results.
（https://mp.weixin.qq.com/s/nr5XyYnsrUUzMRqw4WKGzw）
04 MicroGEM
MicroGEM’s newly launched saliva COVID-19 detection method has been authorized by the FDA for emergency use (19 April 2022)
Recently, the MicroGEM Sal6830 SARS-Cov-2 (hereinafter referred to as "Sal6830") saliva test launched by MicroGEM has obtained emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA). The test method can be used on 27 Provide polymerase chain reaction (PCR) test results at the point of care within minutes.
Sal6830 saliva test is a POC (Point Of Care) testing method based on real-time reverse transcription polymerase chain reaction (RT-PCR). By automating and integrating saliva sample collection, nucleic acid extraction, reverse transcription, real-time PCR amplification and target sequence detection in a simple testing system, rapid, portable, non-invasive SARS-Cov-2 virus detection is achieved.
(https://www.prnewswire.com/news-releases/microgem-granted-emergency-use-authorization-from-fda-for-fast-point-of-care-PCR-covi d-19-saliva-test-301527911.html)
(https://microgembiocovid19.com/how-it-works/)
05 Tessera Therapeutics
Tessera has raised more than US$300 million in Series C financing to advance its gene writing technology (19 April 2022)
Recently, the biotechnology company Tessera Therapeutics announced that it has raised more than US$300 million in Series C financing. Investors include , a wholly-owned subsidiary of Abu Dhabi Investment Authority (ADIA); Alaska Permanent Fund Company; Altitude Life Sciences Ventures; ARTIS Ventures; Cormorant Asset Management; founder of Tessera, Flagship Pioneering; Hanwha Impact Partners; Longevity Vision Fund; March Capital; SALT Fund; SoftBank Vision Fund 2; T. Rowe Price Associates, Inc., and other investors including all of Tessera’s existing institutional shareholders.This round of financing will be used to advance research on Tessera’s unique gene writing technology (GENE WRITING).
（https://www.pharnexcloud.com/zixun/trz_4443）
06 Baifuan Bio
Synthetic biology startup Baifuan Bio completed nearly 50 million yuan in angel round financing (19 April 2022)
Recently, Suzhou Baifuan Enzyme Technology Co., Ltd. completed an angel round of financing of nearly 50 million yuan, led by Sequoia China Seed Fund and followed by Heli Investment. This round of financing will be used for product research and development, building a small trial production line and verifying new processes from grams to kilograms.
Baifuan Bio was founded in 2014 by Professor Xu Jianhe . It has currently established a synthetic biology technology platform, enzyme engineering platform and enzyme-based green synthesis process development technology.
(https://www.vbdata.cn/54742)
07 Hongxin Biotechnology
Hongxin Biotechnology completed angel round financing of 10 million yuan (20 April 2022)
Shenzhen Hongxin Biotechnology Co., Ltd., which focuses on nucleic acid drug delivery and RNA drug research and development, announced the completion of an angel round of financing worth tens of millions of yuan. This round of financing is Zhejiang Tianyu Pharmaceutical Co., Ltd. (a company listed on the Shenzhen Stock Exchange, Stock code: 300702) strategic equity investment in Hongxin Biotech.
（https://mp.weixin.qq.com/s/nr5XyYnsrUUzMRqw4WKGzw）
08 Ginkgo, Bayer & Joyn
Ginkgo has reached a cooperation with Bayer to expand its agricultural biological products platform capabilities (22 April 2022)
Recently, synthetic biology technology company Ginkgo Bioworks announced that it has significantly expanded its platform capabilities in agricultural biological products. This will be achieved through a series of transactions. On the one hand, Ginkgo will acquire Bayer’s 175,000-square-foot biologics R&D site in West Sacramento, including its team and leading development and optimization platform. On the other hand, Ginkgo will also integrate The R&D platform assets of Joyn Bio (Joyn Bio is a joint venture established by Ginkgo and Bayer in 2017). At the same time, Bayer will become a major agricultural customer of Ginkgo's expanded platform and enter into a major new multi-year collaboration that will focus on advancing Joyn's current major nitrogen-fixing microbial projects, as well as new projects in areas such as crop protection and carbon sequestration. project.
While Ginkgo will continue to evaluate the operating expenses required to launch and expand its agricultural capabilities following these transactions, the expected benefits from this multi-year collaboration with Bayer may significantly offset such anticipated expenses. The proposed transaction is expected to close by the end of 2022, pending final agreement and regulatory approval.
（https://www.builtwithbiology.com/read/ginkgo-bioworks-to-expand-platform-capabilities-in-agricultural-biologicals-and-launch-flagship-partnership-with-bayer）
09 SNIPR BIOME
Danish gene therapy company SNIPR’s first microbial drug product enters clinical trials (20 April 2022)
Recently, SNIPR BIOME announced that it has tested the first batch of humans in the Phase I clinical trial of SNIPR001, a CRISPR-based oral therapeutic. Subjects were administered the drug. The purpose of this clinical trial is to investigate the safety and tolerability of SNIPR001 in healthy volunteers and to evaluate the impact of SNIPR001 on reducing E. coli colonization in the intestine. The clinical trial plans to recruit 36 healthy volunteers for multiple ascending doses.
SNIPR001 is an experimental CRISPR therapeutic that selectively targets and eradicates Escherichia coli in the gut, thereby preventing their translocation into the bloodstream in patients with neutropenia and blood cancers.
(https://www.builtwithbiology.com/read/snipr-biome-initiates-first-in-human-clinical-trial-with-snipr001)
cover image comes from the Internet
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Author | Cat Catching Butterflies
Editor | Li Peiyun
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