2010—2019年国家自然科学基金资助合成生物学领域情况

doi:10.12211/2096-8280.2020-065

摘要/Abstract

摘要：

合成生物学以工程化设计理念，对生物体进行有目标的设计、改造乃至重新合成，是生命科学研究的新兴前沿领域。合成生物学研究的技术方法和工具手段，可能突破生命自然进化的限制，通过新颖的研究思路拓展了对生命现象与规律的认识，有望引领生命科学研究的未来。我国科学家在科学基金的资助下围绕染色体人工合成、基因元件、最小基因组构建等研究前沿取得了系列创新成果。本文梳理了2010—2019年期间，科学基金网络信息系统数据库中，国家自然科学基金委合成生物学相关项目的申请及资助情况、获资助项目的主要研究进展、国际合成生物学领域发展规划与布局。据此，分析科学基金资助合成生物学发展面临的挑战，提出合成生物学项目资助管理工作的建议，为相关科研工作者提供参考。

关键词: 科学基金, 合成生物学, 申请与资助, 挑战, 未来发展

Abstract:

Synthetic biology is a cutting-edge research field in life science with engineering concepts, targeted design, transformation and even re-construction of organisms. The technical methods and tools of synthetic biology may break through limit of natural evolution for life. It expands the understanding of life phenomena and laws through novel ideas, which is expected to lead the future of life science research. Chinese scientists have made a series of innovative achievements in the frontiers of chromosome synthesis, genetic element buildup, and minimal genome construction with the support of the National Science Foundation of China (NSFC). This article summarizes the application and funding status of synthetic biology projects from 2010 to 2019 based on the NSFC Network Information System database, as well as,the main research progress and international synthetic biology development planning and layout. Accordingly, it analyzes the challenges in funding synthetic biology research by NSFC, and suggests the management of synthetic biology projects, which provides reference for relevant researchers.

Key words: NSFC, synthetic biology, application and funding status, challenges, future development

中图分类号:

G311

杜全生, 洪伟, 祖岩. 2010—2019年国家自然科学基金资助合成生物学领域情况[J]. 合成生物学, 2020, 1(3): 385-394.

Quansheng DU, Wei HONG, Yan ZU. Grant and funding for synthetic biology at NSFC from 2010 to 2019[J]. Synthetic Biology Journal, 2020, 1(3): 385-394.

图/表 2

参考文献 52

1	WU Y, LI B Z, ZHAO M, et al. Bug mapping and fitness testing of chemically synthesized chromosome X[J]. Science, 2017, 355(6329): aaf4706.
2	XIE Z X, LI B Z, MITCHELL L A, et al. “Perfect” designer chromosome V and behavior of a ring derivative[J]. Science, 2017, 355(6329): eaaf4704.
3	QIN Z, STOILOV P, ZHANG X, et al. SEASTAR: systematic evaluation of alternative transcription start sites in RNA[J].Nucleic Acids Research, 2018, 46(8): e45.
4	CUI J, CUI H, YANG M, et al. Tongue coating microbiome as a potential biomarker for gastritis including precancerous cascade[J]. Protein Cell, 2019, 10(7): 496-509.
5	MIAO Z, DENG K, WANG X, et al. DEsingle for detecting three types of differential expression in single-cell RNA-seq data[J]. Bioinformatics, 2018, 34(18): 3223-3224.
6	CHEN W H, QIN Z J, WANG J, et al. The MASTER (methylation-assisted tailorable ends rational) ligation method for seamless DNA assembly[J]. Nucleic Acids Research, 2013, 41(8): e93.
7	LU AN G, LU X. Tailoring cyanobacterial cell factory for improved industrial properties[J]. Biotechnology Advances, 2018, 36(2): 430-442.
8	LUAN G, ZHANG S, LU X. Engineering Cyanobacteria chassis cells toward more efficient photosynthesis[J]. Current Opinion in Biotechnology, 2020, 62: 1-6.
9	ZHANG L, LIANG Y, WU W, et al. Microbial synthesis of propane by engineering valine pathway and aldehyde-deformylating oxygenase[J]. Biotechnology for Biofuels, 2016, 9(1): 80.
10	LIU W, LUO Z, WANG Y, et al. Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods[J]. Nature Communications, 2018, 9(1): 1936.
11	LIN Y, ZOU X, ZHENG Y, et al. Improving chromosome synthesis with a semiquantitative phenotypic assay and refined assembly strategy[J]. ACS Synthetic Biology, 2019, 8(10): 2203-2211.
12	JIAO Z, FENGHUI QIAN, FENG D, et al. De novo engineering of Corynebacterium glutamicum for l-proline production[J]. ACS Synthetic Biology, 2020, DOI: https://doi.org/10.1021/acssynbio.0c00249. DOI
13	SHAO J, WANG M, YU G, et al. Synthetic far-red light-mediated CRISPR-dCas9 device for inducing functional neuronal differentiation[J]. Proceedings of The National Academy of Sciences of The United States of America, 2018, 115(29): 6722-6730.
14	XIE M, YE H, WANG H, et al. beta-cell-mimetic designer cells provide closed-loop glycemic control[J]. Science, 2016, 354(6317): 1296-1301.
15	ZHANG Z B, WANG Q Y, KE Y X, et al. Design of tunable oscillatory dynamics in a synthetic NF-kappaB signaling circuit[J]. Cell Systems, 2017, 5(5): 460-470.
16	LIU R, ZHU F, LU L, et al. Metabolic engineering of fatty acyl-ACP reductase-dependent pathway to improve fatty alcohol production in Escherichia coli [J]. Metabolic Engineering, 2014, 22: 10-21.
17	GUO D, ZHU J, DENG Z, et al. Metabolic engineering of Escherichia coli for production of fatty acid short-chain esters through combination of the fatty acid and 2-keto acid pathways[J]. Metabolic Engineering, 2014, 22: 69-75.
18	WU T, YE L, ZHAO D, et al. Membrane engineering-A novel strategy to enhance the production and accumulation of beta-carotene in Escherichia coli [J]. Metabolic Engineering, 2017, 43(Pt A): 85-91.
19	LI Q, FAN F, GAO X, et al. Balanced activation of IspG and IspH to eliminate MEP intermediate accumulation and improve isoprenoids production in Escherichia coli [J]. Metabolic Engineering, 2017, 44: 13-21.
20	ZHU X, ZHAO D, QIU H, et al. The CRISPR/Cas9-facilitated multiplex pathway optimization (CFPO) technique and its application to improve the Escherichia coli xylose utilization pathway[J]. Metabolic Engineering, 2017, 43(Pt A): 37-45.
21	GU Y, XU X, WU Y, et al. Advances and prospects of Bacillus subtilis cellular factories: From rational design to industrial applications[J]. Metabolic Engineering, 2018, 50: 109-121.
22	WU Y, CHEN T, LIU Y, et al. Design of a programmable biosensor-CRISPRi genetic circuits for dynamic and autonomous dual-control of metabolic flux in Bacillus subtilis[J]. Nucleic Acids Research, 2020, 48(2):996-1009.
23	NIU T, LIU Y, LI J, et al. Engineering a glucosamine-6-phosphate responsive glmS ribozyme switch enables dynamic control of metabolic flux in Bacillus subtilis for overproduction of N-acetylglucosamine[J]. ACS Synthetic Biology2018, 7(10): 2423-2435.
24	SHAO Y, LU N, XUE X, et al. Creating functional chromosome fusions in yeast with CRISPR-Cas9[J]. Nature Protocols, 2019, 14(8): 2521-2545.
25	ZHANG Y,WEN W H,PU J Y,et al. Extracellularly oxidative activation and inactivation of matured prodrug for cryptic self-resistance in naphthyridinomycin biosynthesis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(44): 11232-11237.
26	LI W N, MA L,SHEN X L,et al. Targeting metabolic driving and intermediate influx in lysine catabolism for high-level glutarate production[J]. Nature Communications, 2019, 10(1): 3337.
27	XU J Y, XU Y, XU Z, et al. Protein acylation is a general regulatory mechanism in biosynthetic pathway of acyl-CoA-derived natural products[J]. Cell Chemical Biology, 2018, 25(8): 984-995.
28	LUO Y Z, LI B Z, LIU D, et al. Engineered biosynthesis of natural products in heterologous hosts[J]. Chemical Society Reviews, 2015, 44(15): 5265-5290.
29	TAN Z T, ZHU C J, FU J W, et al. Regulating cofactor balance in vivo with a synthetic flavin analogue[J]. Angewandte Chemie-International Edition, 2018, 57(50): 16464-16468.
30	CAO W, MA W, WANG X, et al. Enhanced pinocembrin production in Escherichia coli by regulating cinnamic acid metabolism.[J]. Scientific Reports, 2016, 6(1): 32640.
31	LIU Z, LI X, ZHANG J T, et al. Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2[J]. Nature, 2016, 530(7588): 98-102.
32	YU X, QIU W, YANG L, et al. Defining multistep cell fate decision pathways during pancreatic development at single‐cell resolution[J]. The EMBO Journal, 2019, 38(8): e100164.
33	LU Y L,ZHOU Y P, TIAN W D. Combining Hi-C data with phylogenetic correlation to predict the target genes of distal regulatory elements in human genome[J]. Nucleic Acids Research, 2013, 41(22).
34	ZHENG X, CHENG Q, YAO F, et al. Biosynthesis of the pyrrolidine protein synthesis inhibitor anisomycin involves novel gene ensemble and cryptic biosynthetic steps[J]. Proceedings of The National Academy of Sciences of The United States of America, 2017, 114(16):4 135-4140.
35	ZHANG Y, ZOU Y, BROCK N L, et al. Characterization of 2-oxindole forming heme enzyme MarE, expanding the functional diversity of the tryptophan dioxygenase superfamily[J]. Journal of The American Chemical Society, 2017, 139(34): 11887-11894.
36	HUANG T, DUAN Y, ZOU Y, et al. NRPS protein MarQ catalyzes flexible adenylation and specific S-methylation[J].ACS Chemical Biology, 2018, 13(9): 2387-2391.
37	YANG J, JIANG S, LIU X, et al. Aptamer-binding directed DNA origami pattern for logic gates[J]. ACS Applied Materials & Interfaces, 2016, 8(49): 34054-34060.
38	YIN L, GUO X, LIU L, et al. Self-assembled multimeric-enzyme nanoreactor for robust and efficient biocatalysis[J]. ACS Biomaterials Science & Engineering, 2018, 4(6): 2095-2099.
39	HUANG C, YANG C, FANG Z, et al. Discovery of stealthin derivatives and implication of the amidotransferase FlsN3 in the biosynthesis of nitrogen-containing fluostatins[J]. Marine Drugs, 2019, 17(3): 150.
40	ZHANG D, ZHANG F, LIU W, et al. A KAS-III heterodimer in lipstatin biosynthesis nondecarboxylatively condenses C8 and C14 fatty acyl-CoA substrates by a variable mechanism during the establishment of a C22 aliphatic skeleton.[J]. Journal of the American Chemical Society, 2019, 141(9): 3993-4001.
41	WANG J, LIU Y, LIU Y, et al. Time-resolved protein activation by proximal decaging in living systems[J]. Nature, 2019, 569(7757): 509-513.
42	JI Z, NIE Q, YIN Y, et al. Activation and characterization of a cryptic gene cluster reveal two series of aromatic polyketides biosynthesized by divergent tic tailoring pathways[J]. Angewandte Chemie-International Edition,2019, 58: 18046-18054.
43	MA W, CAO W, ZHANG B, et al. Engineering a pyridoxal 5'-phosphate supply for cadaverine production by using Escherichia coli whole-cell biocatalysis[J]. Scientific Reports, 2015, 5(1): 15630-15630.
44	钱万强, 江海燕, 朱庆平, 等. 国内外合成生物学资助体系及产业投入分析[J].中国基础科学, 2014(1): 49-52.
	QIAN W Q, JIANG H Y, ZHU Q P, et al. Analysis of the funding systems and industry investment of synthetic biology in China and main developed countries[J]. China Basic Science, 2014(1): 49-52.
45	杜瑾, 刘夺, 赵广荣, 等. 合成生物学学科发展概况[J].中国科学基金, 2011, 25(3): 143-147.
	DU J, LIU D, ZHAO G R, et al. General situation on the disciplinary development in synthetic biology[J]. Science Foundation in China, 2011, 25(3): 143-147.
46	赵国屏. 合成生物学——生物工程产业化发展的新时期[J].生物产业技术, 2019(1): 2.
	Zhao G P. Synthetic biology——The new era of industrial development of bioengineering[J]. Biotechnology & Business, 2019(1): 2.
47	SLEATOR R D. JCVI-syn3.0-A synthetic genome stripped bare![J]. Bioengineered, 2016, 7(2): 53-56.
48	马延和, 江会锋, 娄春波, 等. 合成生物与生物安全[J].中国科学院院刊, 2016, 31(4): 432-438.
	MA Y H, JIANG H F, LOU C B, et al. Synthetic life and biosecurity[J]. Bulletin of Chinese Academy of Sciences, 2016, 31(4): 432-438.
49	肖尧. 美国国家科学院发布《合成生物学时代的生物防御》报告[J].科技中国, 2018(7): 106-106.
	XIAO R. Biodefense in the age of synthetic biology[J]. China Scitechnology Business, 2018(7): 106.
50	刘晓, 曾艳, 王力为, 等. 创新政策体系保障合成生物学科技与产业发展[J].中国科学院院刊, 2018, 33(11): 1260-1268.
	LIU X, ZENG Y, WANG L W, et al. Innovative policy system to ensure the development of synthetic biology[J]. Bulletin of Chinese Academy of Sciences, 2018, 33(11): 1260-1268.
51	周光明, 陈大明, 熊燕, 等. 英国合成生物学规划及其影响与启示[J].中国细胞生物学学报, 2019, 41(11): 2091-2100.
	ZHOU G M, CHEN D M, XIONG Y, et al. UK synthetic biology strategic planning and its enlightenment[J]. Chinese Journal of Cell Biology, 2019, 41(11): 2091-2100.
52	王璞玥, 唐鸿志, 吴震州, 等. “合成生物学”研究前沿与发展趋势[J].中国科学基金, 2018, 32(5): 545-551.
	WANG P Y, TANG H Z, WU Z Z, et al. Frontiers and trends in synthetic biology[J]. Science Foundation in China, 2018, 32(5): 545-551.

[1]	刁志钿, 王喜先, 孙晴, 徐健, 马波. 单细胞拉曼光谱测试分选装备研制及应用进展[J]. 合成生物学, 2023, 4(5): 1020-1035.
[2]	卢挥, 张芳丽, 黄磊. 合成生物学自动化装置iBioFoundry的构建与应用[J]. 合成生物学, 2023, 4(5): 877-891.
[3]	白仲虎, 任和, 聂简琪, 孙杨. 高通量平行发酵技术的发展与应用[J]. 合成生物学, 2023, 4(5): 904-915.
[4]	吴玉洁, 刘欣欣, 刘健慧, 杨开广, 随志刚, 张丽华, 张玉奎. 基于高通量液相色谱质谱技术的菌株筛选与关键分子定量分析研究进展[J]. 合成生物学, 2023, 4(5): 1000-1019.
[5]	胡哲辉, 徐娟, 卞光凯. 自动化高通量技术在天然产物生物合成中的应用[J]. 合成生物学, 2023, 4(5): 932-946.
[6]	刘欢, 崔球. 原位电离质谱技术在微生物菌株筛选中的应用进展[J]. 合成生物学, 2023, 4(5): 980-999.
[7]	王雁南, 孙宇辉. 碱基编辑技术及其在微生物合成生物学中的应用[J]. 合成生物学, 2023, 4(4): 720-737.
[8]	刘晚秋, 季向阳, 许慧玲, 卢屹聪, 李健. 限制性内切酶的无细胞快速制备研究[J]. 合成生物学, 2023, 4(4): 840-851.
[9]	孙美莉, 王凯峰, 陆然, 纪晓俊. 解脂耶氏酵母底盘细胞的工程改造及应用[J]. 合成生物学, 2023, 4(4): 779-807.
[10]	孙智, 杨宁, 娄春波, 汤超, 杨晓静. 功能拓扑的理性设计及其在合成生物学中的应用[J]. 合成生物学, 2023, 4(3): 444-463.
[11]	赖奇龙, 姚帅, 查毓国, 白虹, 宁康. 微生物组生物合成基因簇发掘方法及应用前景[J]. 合成生物学, 2023, 4(3): 611-627.
[12]	孟巧珍, 郭菲. “可折叠性”在酶智能设计改造中的应用研究——以AlphaFold2为例[J]. 合成生物学, 2023, 4(3): 571-589.
[13]	王晟, 王泽琛, 陈威华, 陈珂, 彭向达, 欧发芬, 郑良振, 孙瑨原, 沈涛, 赵国屏. 基于人工智能和计算生物学的合成生物学元件设计[J]. 合成生物学, 2023, 4(3): 422-443.
[14]	吕海龙, 王建, 吕浩, 王金, 徐勇, 顾大勇. 合成生物学在下一代基因诊断技术中的应用进展[J]. 合成生物学, 2023, 4(2): 318-332.
[15]	申赵铃, 吴艳玲, 应天雷. 合成生物学与病毒疫苗研发[J]. 合成生物学, 2023, 4(2): 333-346.