Biosafety Risks and Countermeasures of Active Substance in Synthesis Biology

doi:10.13523/j.cb.2209068

China Biotechnology

2023, Vol. 43

Issue (2/3): 180-189 DOI: 10.13523/j.cb.2209068

Biosafety Risks and Countermeasures of Active Substance in Synthesis Biology

NING Jun-tao¹,ZOU Shi-shi²,ZUO Kun-lan³,WU Zong-zhen³,Li Jing⁴,XU Yan-long⁵,LIU Huan^3,^6,^**(

)

1 Intellectual Property Development & Research Center, China National Intellectual Property Administration, Beijing 100088, China
2 Wuhan University, Wuhan 430072, China
3 School of Humanities and Social Sciences, University of Science and Technology of China, Hefei 230026, China
4 Office of Laboratory Management, Chinese Center for Disease Control and Prevention, Beijing 102206, China
5 College of Humanities, University of Chinese Academy of Sciences, Beijing 100049, China
6 Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

Download:

HTML

PDF(525KB) HTML
Export: BibTeX | EndNote (RIS)

Abstract

Active substances are often synthesized by microorganisms as carriers in biological metabolic engineering at all times, and the formation of metabolites in all stages of the life system provides a natural template and design blueprint for the development of synthetic biotechnology. If these metabolites involve harmful active substances or potential safety threats, such as toxins and protein complexes that are toxic to humans, animals and plants, drug molecules and their derivatives that can be used for clinical treatment and can also lead to dysfunction and health hazards, and chemicals that are prohibited or restricted by international conventions, they will have adverse effects on biosafety. Through reviewing and analyzing the safety risks in synthetic biology related to active substances such as natural metabolic pathway biosynthetic active substances, non-natural metabolic pathway biosynthetic active substances, chemosynthetic active substances and active substance delivery technology, this paper puts forward countermeasure strategy for promoting the innovative development and application fields of active substances in synthetic biology.

Key words： Biosafety Synthetic biology Active substance

Received: 26 September 2022 Published: 31 March 2023

ZTFLH:

Q819

Corresponding Authors: **Huan LIU E-mail: liuhuan520@ustc.edu.cn

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	Jun-tao NING
	Shi-shi ZOU
	Kun-lan ZUO
	Zong-zhen WU
	Jing Li
	Yan-long XU
	Huan LIU

Cite this article:

NING Jun-tao, ZOU Shi-shi, ZUO Kun-lan, WU Zong-zhen, Li Jing, XU Yan-long, LIU Huan. Biosafety Risks and Countermeasures of Active Substance in Synthesis Biology. China Biotechnology, 2023, 43(2/3): 180-189.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2209068 OR https://manu60.magtech.com.cn/biotech/Y2023/V43/I2/3/180


[1]	高磊, 于欣水, 雷晓光. 天然产物生物合成:探索大自然合成次生代谢产物的奥秘. 大学化学, 2019, 34(12): 45-53.

[1]	Gao L, Yu X S, Lei X G. Biosynthesis of natural products: exploring the secret of how nature produces the secondary metabolites. University Chemistry, 2019, 34(12): 45-53.

[2]	Pyne M E, Kevvai K, Grewal P S, et al. A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids. Nature Communications, 2020, 11: 3337. doi: 10.1038/s41467-020-17172-x pmid: 32620756

[3]	Nakagawa A, Minami H, Kim J S, et al. A bacterial platform for fermentative production of plant alkaloids. Nature Communications, 2011, 2: 326. doi: 10.1038/ncomms1327 pmid: 21610729

[4]	DeLoache W C, Russ Z N, Narcross L, et al. An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nature Chemical Biology, 2015, 11(7): 465-471. doi: 10.1038/nchembio.1816 pmid: 25984720

[5]	Jamieson C S, Misa J, Tang Y, et al. Biosynthesis and synthetic biology of psychoactive natural products. Chemical Society Reviews, 2021, 50(12): 6950-7008. doi: 10.1039/d1cs00065a pmid: 33908526

[6]	Tehran D A, Pirazzini M. Novel botulinum neurotoxins: exploring underneath the iceberg tip. Toxins, 2018, 10(5): 190. doi: 10.3390/toxins10050190

[7]	Masuyer G, Chaddock J A, Foster K A, et al. Engineered botulinum neurotoxins as new therapeutics. Annual Review of Pharmacology and Toxicology, 2014, 54: 27-51. doi: 10.1146/annurev-pharmtox-011613-135935 pmid: 24016211

[8]	陈振. 基于非天然途径的二元醇绿色生物合成//中国生物工程学会青年工作委员会. 中国生物工程学会第二届青年科技论坛暨首届青年工作委员会学术年会摘要集. 2017: 93.

[8]	Chen Z. Green biosynthesis of diols based on unnatural pathways//Youth Working Committee on Chinese Society of Biotechnology. Proceedings of China Society of Biotechnology Young Scientists Forum Ⅱ. 2017: 93.

[9]	Jacquet P, Rémy B, Bross R P T, et al. Enzymatic decontamination of G-type, V-type and novichok nerve agents. International Journal of Molecular Sciences, 2021, 22(15): 8152. doi: 10.3390/ijms22158152

[10]	Job L, Köhler A, Escher B, et al. A catalytic bioscavenger with improved stability and reduced susceptibility to oxidation for treatment of acute poisoning with neurotoxic organophosphorus compounds. Toxicology Letters, 2020, 321: 138-145. doi: S0378-4274(19)30424-2 pmid: 31891759

[11]	Lee N R, Yun H, Lee C, et al. Engineered recombinant PON1-OPH fusion hybrids: potentially effective catalytic bioscavengers against organophosphorus nerve agent analogs. Journal of Microbiology and Biotechnology, 2021, 31(1): 144-153. doi: 10.4014/jmb.2006.06044 pmid: 33144547

[12]	Bzdrenga J, Trenet E, Chantegreil F, et al. A thermophilic bacterial esterase for scavenging nerve agents: a kinetic, biophysical and structural study. Molecules (Basel, Switzerland), 2021, 26(3): 657. doi: 10.3390/molecules26030657

[13]	Song T Y, Wang F L, Xiong S S, et al. Surface display of organophosphorus-degrading enzymes on the recombinant spore of Bacillus subtilis. Biochemical and Biophysical Research Communications, 2019, 510(1): 13-19. doi: 10.1016/j.bbrc.2018.12.077

[14]	Pandit A V, Srinivasan S, Mahadevan R. Redesigning metabolism based on orthogonality principles. Nature Communications, 2017, 8: 15188. doi: 10.1038/ncomms15188 pmid: 28555623

[15]	Yim H, Haselbeck R, Niu W, et al. Metabolic engineering of Escherichia coli for direct production of 1, 4-butanediol. Nature Chemical Biology, 2011, 7(7): 445-452. doi: 10.1038/nchembio.580

[16]	张金宏, 崔志勇, 祁庆生, 等. 解脂耶氏酵母表达调控工具的开发及天然产物合成的研究进展. 生物工程学报, 2022, 38(2): 478-505.

[16]	Zhang J H, Cui Z Y, Qi Q S, et al. The recent advances in developing gene editing and expression tools and the synthesis of natural products in Yarrowia lipolytica. Chinese Journal of Biotechnology, 2022, 38(2): 478-505.

[17]	Groenewald M, Boekhout T, Neuvéglise C, et al. Yarrowia lipolytica: safety assessment of an oleaginous yeast with a great industrial potential. Critical Reviews in Microbiology, 2014, 40(3): 187-206. doi: 10.3109/1040841X.2013.770386 pmid: 23488872

[18]	Arias-Gómez A, Godoy A, Portilla J. Functional pyrazolo[1, 5-a]pyrimidines: current approaches in synthetic transformations and uses As an antitumor scaffold. Molecules (Basel, Switzerland), 2021, 26(9): 2708. doi: 10.3390/molecules26092708

[19]	He H Y, Zhao J N, Jia R, et al. Novel pyrazolo[3, 4-d]pyrimidine derivatives as potential antitumor agents: exploratory synthesis, preliminary structure-activity relationships, and in vitro biological evaluation. Molecules (Basel, Switzerland), 2011, 16(12): 10685-10694. doi: 10.3390/molecules161210685

[20]	Rango E, D’Antona L, Iovenitti G, et al. Si113-prodrugs selectively activated by plasmin against hepatocellular and ovarian carcinoma. European Journal of Medicinal Chemistry, 2021, 223: 113653. doi: 10.1016/j.ejmech.2021.113653

[21]	Radi M, Dreassi E, Brullo C, et al. Design, synthesis, biological activity, and ADME properties of pyrazolo[3, 4-d]pyrimidines active in hypoxic human leukemia cells: a lead optimization study. Journal of Medicinal Chemistry, 2011, 54(8): 2610-2626. doi: 10.1021/jm1012819

[22]	D’Antona L, Dattilo V, Catalogna G, et al. In preclinical model of ovarian cancer, the SGK 1 inhibitor SI113 counteracts the development of paclitaxel resistance and restores drug sensitivity. Translational Oncology, 2019, 12(8): 1045-1055. doi: 10.1016/j.tranon.2019.05.008

[23]	Åstrand A, Guerrieri D, Vikingsson S, et al. In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT1A, and 5-HT2A receptors: on-target receptor potency and efficacy, and off-target effects. Forensic Science International, 2020, 317: 110553. doi: 10.1016/j.forsciint.2020.110553

[24]	Gee P, Schep L J, Jensen B P, et al. Case series: toxicity from 25B-NBOMe: a cluster of N-bomb cases. Clinical Toxicology (Philadelphia, Pa), 2016, 54(2): 141-146.

[25]	Poulie C B M, Jensen A A, Halberstadt A L, et al. DARK classics in chemical neuroscience: NBOMes. ACS Chemical Neuroscience, 2019, 11(23): 3860-3869. doi: 10.1021/acschemneuro.9b00528

[26]	Wagmann L, Richter L H J, Kehl T, et al. In vitro metabolic fate of nine LSD-based new psychoactive substances and their analytical detectability in different urinary screening procedures. Analytical and Bioanalytical Chemistry, 2019, 411(19): 4751-4763. doi: 10.1007/s00216-018-1558-9 pmid: 30617391

[27]	Ai Y J, Xie R X, Xiong J L, et al. Microfluidics for biosynthesizing: from droplets and vesicles to artificial cells. Small (Weinheim an Der Bergstrasse, Germany), 2020, 16(9): e1903940.

[28]	Dallinger D, Gutmann B, Kappe C O. The concept of chemical generators: on-site on-demand production of hazardous reagents in continuous flow. Accounts of Chemical Research, 2020, 53(7): 1330-1341. doi: 10.1021/acs.accounts.0c00199 pmid: 32543830

[29]	Rudokas M, Najlah M, Albed Alhnan M, et al. Liposome delivery systems for inhalation: a critical review highlighting formulation issues and anticancer applications. Medical Principles and Practice, 2016, 25(Suppl. 2): 60-72. doi: 10.1159/000445116

[30]	Qiu Y S, Man R C H, Liao Q Y, et al. Effective mRNA pulmonary delivery by dry powder formulation of PEGylated synthetic KL4 peptide. Journal of Controlled Release, 2019, 314: 102-115. doi: S0168-3659(19)30591-7 pmid: 31629037

[31]	Willaert W, Sessink P, Ceelen W. Occupational safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC). Pleura and Peritoneum, 2017, 2(3): 121-128. doi: 10.1515/pp-2017-0018 pmid: 30911641

[32]	Lindsay K E, Vanover D, Thoresen M, et al. Aerosol delivery of synthetic mRNA to vaginal mucosa leads to durable expression of broadly neutralizing antibodies against HIV. Molecular Therapy: the Journal of the American Society of Gene Therapy, 2020, 28(3): 805-819. doi: 10.1016/j.ymthe.2020.01.002

[33]	Rezvani M, Mohammadnejad J, Narmani A, et al. Synthesis and in vitro study of modified chitosan-polycaprolactam nano complex as delivery system. International Journal of Biological Macromolecules, 2018, 113: 1287-1293. doi: S0141-8130(17)35025-0 pmid: 29481956

[34]	Gupta R, Chen Y, Xie H. In vitro dissolution considerations associated with nano drug delivery systems. WIREs Nanomedicine and Nanobiotechnology, 2021, 13(6): e1732.

[35]	Scher G, Schnell M J. Rhabdoviruses as vectors for vaccines and therapeutics. Current Opinion in Virology, 2020, 44: 169-182. doi: 10.1016/j.coviro.2020.09.003 pmid: 33130500

[36]	Rahbarghazi R, Jabbari N, Sani N A, et al. Tumor-derived extracellular vesicles: reliable tools for Cancer diagnosis and clinical applications. Cell Communication and Signaling: CCS, 2019, 17(1): 73. doi: 10.1186/s12964-019-0390-y

[37]	Wang J, Chen D, Ho E A. Challenges in the development and establishment of exosome-based drug delivery systems. Journal of Controlled Release, 2021, 329: 894-906. doi: 10.1016/j.jconrel.2020.10.020 pmid: 33058934

[38]	Huang X L, Zhuang J, Teng X, et al. The promotion of human malignant melanoma growth by mesoporous silica nanoparticles through decreased reactive oxygen species. Biomaterials, 2010, 31(24): 6142-6153. doi: 10.1016/j.biomaterials.2010.04.055 pmid: 20510446

[39]	He Q J, Zhang Z W, Gao Y, et al. Intracellular localization and cytotoxicity of spherical mesoporous silica nano- and microparticles. Small (Weinheim an Der Bergstrasse, Germany), 2009, 5(23): 2722-2729. doi: 10.1002/smll.v5:23

[40]	李晓军, 张万斌, 高栓虎. 复杂天然产物全合成: 化学合成与生物合成结合的策略. 有机化学, 2018, 38(9): 2185-2198. doi: 10.6023/cjoc201806019

[40]	Li X J, Zhang W B, Gao S H. Total synthesis of complex natural products: combination of chemical synthesis and biosynthesis strategies. Chinese Journal of Organic Chemistry, 2018, 38(9): 2185-2198. doi: 10.6023/cjoc201806019

[41]	沈秀敏, 毛淑梅. 对基因工程技术的辩证分析. 医学与社会, 2001, 14(6): 35-37.

[41]	Shen X M, Mao S M. The dialectical analysis of genetic engineering technique. Medicine and Society, 2001, 14(6): 35-37.

[42]	王凯峰, 王金鹏, 韦萍, 等. 代谢工程改造解脂耶氏酵母生产脂肪酸及其衍生物. 化工学报, 2021, 72(1): 351-365. doi: 10.11949/0438-1157.20201043

[42]	Wang K F, Wang J P, Wei P, et al. Metabolic engineering of Yarrowia lipolytica to produce fatty acids and their derivatives. CIESC Journal, 2021, 72(1): 351-365. doi: 10.11949/0438-1157.20201043

[43]	Wong L, Engel J, Jin E Q, et al. YaliBricks, a versatile genetic toolkit for streamlined and rapid pathway engineering in Yarrowia lipolytica. Metabolic Engineering Communications, 2017, 5: 68-77. doi: 10.1016/j.meteno.2017.09.001

[44]	Lee S K, Chou H, Ham T S, et al. Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels. Current Opinion in Biotechnology, 2008, 19(6): 556-563. doi: 10.1016/j.copbio.2008.10.014 pmid: 18996194

[45]	冯长启, 卢彩虹, 郭红艳, 等. 简述与《禁止化学武器公约》相关的生化融合技术. 国防科技, 2014, 35(2): 53-55, 52.

[45]	Feng C Q, Lu C H, Guo H Y, et al. Discussion of the technics of convergence between chemistry and biology related to the chemical weapons convention. National Defense Science & Technology, 2014, 35(2): 53-55, 52.

[46]	刘磊, 黄卉. 尼克松政府对生化武器的政策与《禁止生物武器公约》. 史学月刊, 2014(4): 62-71, 136.

[46]	Liu L, Huang H. The Nixon administration’s policy on biological and chemical weapons and the biological weapons convention. Journal of Historical Science, 2014(4): 62-71, 136.

[47]	Alshawwa S Z, Kassem A A, Farid R M, et al. Nanocarrier drug delivery systems: characterization, limitations, future perspectives and implementation of artificial intelligence. Pharmaceutics, 2022, 14(4): 883. doi: 10.3390/pharmaceutics14040883

[48]	马延和, 江会锋, 娄春波, 等. 合成生物与生物安全. 中国科学院院刊, 2016, 31(4): 432-438.

[48]	Ma Y H, Jiang H F, Lou C B, et al. Synthetic life and biosecurity. Bulletin of Chinese Academy of Sciences, 2016, 31(4): 432-438.

[1]	YANG Yang, YAO Ming-dong, WANG Ying, XIAO Wen-hai. Research Progress of Synthesis of 2'-Fucosyllactose by Yeast[J]. China Biotechnology, 2023, 43(1): 127-138.

[2]	GUO Yan-tong,LIU Zhong-ming,ZHANG Hai-yan,ZHANG Bao. Molecular Diagnostic POCT Technology and Its Application in Emerging Infectious Diseases[J]. China Biotechnology, 2022, 42(9): 50-57.

[3]	Xue-xia ZENG,Yu DAN,Shao-ming MAO,Jia-hui SUN,Guo-dong LUAN,Xue-feng LV. Research Progress on the Cyanobacterial Photosynthetic Production of Sugars Utilizing Carbon Dioxide[J]. China Biotechnology, 2022, 42(7): 90-100.

[4]	ZHANG Da-lu,GE Qi,FENG Yi-bo,CHEN Wei-gang. Comparison and Analysis on Scientific Research Programs on DNA Data Storage[J]. China Biotechnology, 2022, 42(6): 116-129.

[5]	BAI Song,HOU Zheng-jie,GAO Geng-rong,QIAO Bin,CHENG Jing-sheng. Advances in the Synthesis of Odd-chain Fatty Acids by Microorganisms[J]. China Biotechnology, 2022, 42(6): 76-85.

[6]	LIANG Shi-yu,WAN Li,GUO Xiao-jia,WANG Xue-ying,LV Li-ting,HU Ying-han,ZHAO Zong-bao. *Engineered Rhodosporidium toruloides* Strains Capable of Biosynthesizing a Non-natural Cofactor**[J]. China Biotechnology, 2022, 42(5): 58-68.

[7]	ZHAO Chi-hong,SU Dan-dan,LI Chun,WU Zong-zhen,ZUO Kun-lan,XU Yan-long,LIU Huan. Synthetic Biology Risks and Biosafety Strategies in the View of Overall National Security Concept[J]. China Biotechnology, 2022, 42(12): 120-128.

[8]	Chun-li HAN,Han-jie WANG. Advances of Engineered Live Biotherapeutics in Tumor Immunotherapy[J]. China Biotechnology, 2022, 42(10): 39-50.

[9]	Hui-min LI,Bin JIA,Xia LI,Duo LIU. Advances in Engineering Yeast Chassis for Producing Aromatic Compounds[J]. China Biotechnology, 2022, 42(10): 80-92.

[10]	MA Ning,WANG Han-jie. Advances of Optogenetics in the Regulation of Bacterial Production[J]. China Biotechnology, 2021, 41(9): 101-109.

[11]	HUANG Huan-bang,WU Yang,YANG You-hui,WANG Zhao-guan,QI Hao. Progress in Incorporation of Non-canonical Amino Acid Based on Archaeal Tyrosyl-tRNA Synthetase[J]. China Biotechnology, 2021, 41(9): 110-125.

[12]	GUO Man-man,TIAN Kai-ren,QIAO Jian-jun,LI Yan-ni. Application of Phage Recombinase Systems in Synthetic Biology[J]. China Biotechnology, 2021, 41(8): 90-102.

[13]	DONG Shu-xin,QIN Lei,LI Chun,LI Jun. Transcription Factor Engineering Harnesses Metabolic Networks to Meet Efficient Production in Cell Factories[J]. China Biotechnology, 2021, 41(4): 55-63.

[14]	MA Li-li,YI Pan-pan,AO Ni-hua,JIAO Hong-tao,LEI Rui-peng,LIU Huan. A Study of Interdisciplinarity in Biosafety Research Based on Discipline Categories and Enrichment Analysis[J]. China Biotechnology, 2021, 41(12): 116-124.

[15]	ZHENG Yi,GUO Shi-ying,SUI Feng-xiang,YANG Qi-yu,WEI Ya-xuan,LI Xiao-yan. Applications of Quorum Sensing Systems in Synthetic Biology[J]. China Biotechnology, 2021, 41(11): 100-109.

Viewed

Full text

Abstract

Cited

Shared

Discussed