genes functional identification and synthetic biology of

2
Genes functional identification and synthetic biology of natural products GAO Wei 1* , HUANG Lu-Qi 2* 1 School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 2 State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China Available online 20 Sep., 2020 [CLC Number] R284 [Document code] A [Article ID] 2095-6975(2020)09-0641-02 There are many kinds of natural products, some of them play important roles in plant physiology and biochemistry (e.g. gibberellins, sterols), and some of them have good phar- macological activities for clinical application (e.g. tan- shinone, ginsenosides). For the past few years, the biosyn- thetic pathway of many natural products had been com- pletely analyzed, such as ginsenosides [1] , vincristine [2, 3] and saponins [4] . And many great achievements also had been made in the analysis of the biosynthetic pathway of other nat- ural products, such as tanshinone [5] , triptolide [6] and celast- rol [7] . Nevertheless, the analysis of biosynthetic pathway of natural products also faces many challenges. The develop- ment of genome, transcriptome and correlation analysis of metabonomics provide effective methods for the analysis of biosynthetic pathway, such as the exploration of gene clusters in genome [8, 9] . The biosynthesis pathway of natural products make a contribution to the research and sustainable utiliza- tion of them [10] , and also provides an effective method for the study of chemical diversity of them [11] . Finally, synthetic bio- logy can not only be the base of the heterologous reconstruc- tion of biosynthetic pathway of natural products, but also be- come a tool for understanding biological evolution. Gene is one of the key factors which determine biological traits, in re- cent years, we gain new perspective for studying the system- ic evolution of organisms, through the analysis of the key gene SNP sites of the biosynthetic pathway [12] . In this issue of Chinese Journal of Natural Medicines (CJNM), we are pleased to publish five articles describe the analysis and reconstruction of natural products biosynthetic pathway. Zhao et al. [13] reviewed the biosynthesis of ginsen- osides, 4 glycosyltransferases play essential roles in the form- ation on ginsenosides, makes them important bioparts for synthetic biology-based production of these valuable ginsen- osides. Wang et al. [14] reported the isolation and identifica- tion of nine oxidosqualene cyclases (ApOSC3-11) from An- drographis paniculata for the first time. Li et al. [15] made the activities improved of β-carotene ketolase and β-carotene hy- droxylase for conversion of β-carotene to astaxanthin with higher efficiency, through constructing crtW mutation, balan- cing the expression levels between crtW* and crtZ, and in- creasing the copy number of the balanced crtW*−crtZ cas- sette. Wang et al. [16] described that the inthomycin B and its two new analogues were isolated from the crude extract of Streptomyces pactum L8. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was pro- posed via an oxidative release of the assembly chain assisted by the P450 domain. In the fifth paper [17] , the author de- scribed that 22 candidate cytochrome P450 genes and 15 can- didate dirigent proteins genes were discovered based on the transcriptome sequencing, and the accumulation patterns of 30 metabolites involved in the lignan pathway were studied based on the metabonomic analysis. Synthetic biology is one of the rapid developing scientif- ic fields in recent years. Through synthetic biology, we have a better understanding of the natural synthesis process of nat- ural products [18] , which provides a favorable method to re- search the diversity of natural products, and also provides new tools for us to create new approach for producing natur- al products, we can synthesize compounds with different structures by artificial combination of different synthesis modules [19, 20] . Today, synthetic biology has been applied in different fields, such as producing drugs, biofuels and bioma- terials from cheap carbon sources [21] . Meanwhile, with the continuous development and progress of synthetic biology over the past few years, it has been applied in many fields such as metabolic engineering, biological evolution and so [Received on] 10-Aug.-2020 [ * Corresponding author] E-mails: [email protected] (GAO Wei); [email protected] (HUANG Lu-Qi) These authors have no conflict of interest to declare. Available online at www.sciencedirect.com Chinese Journal of Natural Medicines 2020, 18(9): 641-642 doi: 10.1016/S1875-5364(20)60002-4 •Editorial• – 641 –

Upload: others

Post on 03-Dec-2021

7 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Genes functional identification and synthetic biology of

Genes functional identification and synthetic biology ofnatural products

GAO Wei1*, HUANG Lu-Qi2*

1 School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China;2 State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academyof Chinese Medical Sciences, Beijing 100700, China

Available online 20 Sep., 2020

[CLC Number] R284 [Document code] A [Article ID] 2095-6975(2020)09-0641-02

There are many kinds of natural products, some of themplay important roles in plant physiology and biochemistry(e.g. gibberellins, sterols), and some of them have good phar-macological activities for clinical application (e.g. tan-shinone, ginsenosides). For the past few years, the biosyn-thetic pathway of many natural products had been com-pletely analyzed, such as ginsenosides [1], vincristine [2, 3] andsaponins [4]. And many great achievements also had beenmade in the analysis of the biosynthetic pathway of other nat-ural products, such as tanshinone [5], triptolide [6] and celast-rol [7]. Nevertheless, the analysis of biosynthetic pathway ofnatural products also faces many challenges. The develop-ment of genome, transcriptome and correlation analysis ofmetabonomics provide effective methods for the analysis ofbiosynthetic pathway, such as the exploration of gene clustersin genome [8, 9]. The biosynthesis pathway of natural productsmake a contribution to the research and sustainable utiliza-tion of them [10], and also provides an effective method for thestudy of chemical diversity of them [11]. Finally, synthetic bio-logy can not only be the base of the heterologous reconstruc-tion of biosynthetic pathway of natural products, but also be-come a tool for understanding biological evolution. Gene isone of the key factors which determine biological traits, in re-cent years, we gain new perspective for studying the system-ic evolution of organisms, through the analysis of the keygene SNP sites of the biosynthetic pathway [12].

In this issue of Chinese  Journal  of  Natural  Medicines(CJNM), we are pleased to publish five articles describe theanalysis and reconstruction of natural products biosyntheticpathway. Zhao et al. [13] reviewed the biosynthesis of ginsen-osides, 4 glycosyltransferases play essential roles in the form-

ation on ginsenosides, makes them important bioparts forsynthetic biology-based production of these valuable ginsen-osides. Wang et  al. [14] reported the isolation and identifica-tion of nine oxidosqualene cyclases (ApOSC3-11) from An-drographis paniculata for the first time. Li et al. [15] made theactivities improved of β-carotene ketolase and β-carotene hy-droxylase for conversion of β-carotene to astaxanthin withhigher efficiency, through constructing crtW mutation, balan-cing the expression levels between crtW* and crtZ, and in-creasing the copy number of the balanced crtW*−crtZ cas-sette. Wang et al. [16] described that the inthomycin B and itstwo new analogues were isolated from the crude extract ofStreptomyces pactum L8. Combined with the gene deletion ofthe rare P450 domain in the NRPS module, a formationmechanism of carboxamide moiety in inthomycins was pro-posed via an oxidative release of the assembly chain assistedby the P450 domain. In the fifth paper [17], the author de-scribed that 22 candidate cytochrome P450 genes and 15 can-didate dirigent proteins genes were discovered based on thetranscriptome sequencing, and the accumulation patterns of30 metabolites involved in the lignan pathway were studiedbased on the metabonomic analysis.

Synthetic biology is one of the rapid developing scientif-ic fields in recent years. Through synthetic biology, we havea better understanding of the natural synthesis process of nat-ural products [18], which provides a favorable method to re-search the diversity of natural products, and also providesnew tools for us to create new approach for producing natur-al products, we can synthesize compounds with differentstructures by artificial combination of different synthesismodules [19, 20]. Today, synthetic biology has been applied indifferent fields, such as producing drugs, biofuels and bioma-terials from cheap carbon sources [21]. Meanwhile, with thecontinuous development and progress of synthetic biologyover the past few years, it has been applied in many fieldssuch as metabolic engineering, biological evolution and so

[Received on] 10-Aug.-2020[*Corresponding author] E-mails: [email protected] (GAOWei); [email protected] (HUANG Lu-Qi)These authors have no conflict of interest to declare.

Available online at www.sciencedirect.com

Chinese Journal of Natural Medicines 2020, 18(9): 641-642doi: 10.1016/S1875-5364(20)60002-4

•Editorial•

– 641 –

Page 2: Genes functional identification and synthetic biology of

on. This time, we collected five articles on the application ofsynthetic biology in biosynthetic pathway of natural products,engineering bacteria modification, and compound diversity.We hope that the articles to promote the cooperation of ex-perts on the application of synthetic biology in various fields.

References Li L, Lee SJ, Yuan QP, et al. Production of bioactive ginsenos-ide Rg3(S) and compound K using recombinant Lactococcuslactis [J]. J Ginseng Res, 2018, 42(4): 412-418.

[1]

Qu Y, Easson MEAM, Simionescu R, et  al. Solution of themultistep pathway for assembly of corynanthean, strychnos,iboga, and aspidosperma monoterpenoid indole alkaloids from19E-geissoschizine [J]. PNAS, 2018, 115: 12.

[2]

Caputi L, Franke J, Farrow SC, et  al. Missing enzymes in thebiosynthesis of the anticancer drug vinblastine in Madagascarperiwinkle [J]. Science, 2018, 360(6394): 1235-1239.

[3]

Mo GY, Huang F, Fang Y, et  al. Transcriptomic analysis inAnemone flaccida rhizomes reveals ancillary pathway for triter-pene saponins biosynthesis and differential responsiveness tophytohormones [J]. Chin J Nat Med, 2019, 17(2): 131-144.

[4]

Guo J, Ma X, Cai Y, et al. Cytochrome P450 promiscuity leadsto a bifurcating biosynthetic pathway for tanshinones [J]. NewPhytol, 2016, 210(2): 525-534.

[5]

Tu L, Su P, Zhang Z, et al. Genome of Tripterygium wilfordiiand identification of cytochrome P450 involved in triptolidebiosynthesis [J]. Nat Commun, 2020, 11(1): 971.

[6]

Zhou JW, Hu TY, Gao LH, et al. Friedelane-type triterpene cy-clase in celastrol biosynthesis from Tripterygium wilfordii andits application for triterpenes biosynthesis in yeast [J]. NewPhytol, 2019, 223(2): 722-735.

[7]

Kjaerbolling I, Vesth TC, Frisvad JC, et al. Linking secondarymetabolites to gene clusters through genome sequencing of sixdiverse Aspergillus species [J]. Proc  Natl  Acad  Sci  U  S  A,2018, 115(4): E753-E761.

[8]

Mao L, Kawaide H, Higuchi T, et  al. Genomic evidence forconvergent evolution of gene clusters for momilactone biosyn-thesis in land plants [J]. Proc  Natl  Acad  Sci  U  S  A, 2020,117(22): 12472-12480.

[9]

Yin Y, Li Y, Jiang D, et al. De novo biosynthesis of liquiritinin Saccharomyces cerevisiae [J]. Acta  Pharm  Sin  B, 2020,10(4): 711-721.

[10]

Qu C, Yin N, Chen S, et al. Comparative analysis of the meta-bolic profiles of yellow-versus black-seeded rapeseed usingUPLC-HESI-MS/MS and transcriptome analysis [J]. J  AgricFood Chem, 2020, 68(10): 3033-3049.

[11]

Li H, Thrash A, Tang JD, et  al. Leveraging GWAS data toidentify metabolic pathways and networks involved in maizelipid biosynthesis [J]. Plant J, 2019, 98(5): 853-863.

[12]

Zhao JN, Wang RF, Zhao SJ, et al. Advance in glycosyltrans-ferases, the important bioparts for production of diversified gin-senosides [J]. Chin J Nat Med, 2020, 18(9): 634-658.

[13]

Wang J, Lin HX, Zhao H, et  al. Molecular cloning and func-tional characterization of multiple ApOSCs from Andrograph-is paniculata [J]. Chin J Nat Med, 2020, 18(9): 659-665.

[14]

Li D, Li Y, Xu JY, et  al. Engineering CrtW and CrtZ for im-proving biosynthesis of astaxanthin in Escherichia  coli [J].Chin J Nat Med, 2020, 18(9): 666-676.

[15]

Wang YJ, Wang L, He X, et  al. Characterization of inthomy-cin biosynthetic gene cluster revealing new insights into car-boxamide formation [J]. Chin J Nat Med, 2020, 18(9): 677-683.

[16]

Chen CY, Liu SY, Yan Y, et  al. Candidate genes involved inthe biosynthesis of lignan in Schisandra  chinensis fruit basedon transcriptome and Metabolomes analysis [J]. Chin  J  NatMed, 2020, 18(9): 684-695.

[17]

Tong YR, Su P, Guan HY, et  al. Eudesmane-type sesquiter-pene diols directly synthesized by a sesquiterpene cyclase inTripterygium  wilfordii [J]. Biochem  J, 2018, 475(17): 2713-2725.

[18]

Mafu S, Jia M, Zi J, et  al. Probing the promiscuity of ent-kaurene oxidases via combinatorial biosynthesis [J]. Proc NatlAcad Sci U S A, 2016, 113(9): 2526-2531.

[19]

Lee N, Hwang S, Lee Y, et al. Synthetic biology tools for nov-el secondary metabolite discovery in streptomyces [J]. J Micro-biol Biotechnol, 2019, 29(5): 667-686.

[20]

Choi KR, Jang WD, Yang D, et  al. Systems metabolic engin-eering strategies: integrating systems and synthetic biologywith metabolic engineering [J]. Trends Biotechnol, 2019, 37(8):817-837.

[21]

Cite this article as: GAO Wei, HUANG Lu-Qi. Genes functional identification and synthetic biology of natural products [J].Chin J Nat Med, 2020, 18(9): 641-642.

Dr. GAO Wei is a professor and the dean of School of Pharmaceutical Sciences, Capital Medical University.He was selected into the Chang Jiang Scholars Program by the Ministry of Education and the National High-levelPersonnel of Special Support Program. He was funded by National Natural Science Foundation for OutstandingY-outh Foundation, China. Dr. Gao’s research interests focus on natural medicinal resources and molecular pharma-cognosy, especially the biosynthesis and physiological function of terpenoid natural products from chinese herbalmedicine. He has published over 80 papers, among which 48 SCI papers were published in Nature Communica-tions, JACS, New Phytologist, etc.

Prof. HUANG Lu-Qi is an academician of Chinese Academy of Engineering, the president of China Academyof Chinese Medical Sciences, a leading researcher and the group leader of the experts guiding group for the na-tional survey on Chinese Medicinal Material Resources, the head of Chinese Medicinal Material Resources Innov-ation Team of Key Area issued by Ministry of Science and Technology, former Chief Scientist of national 973plan project. He won the second prize of State Science and Technology Progress Award as the first completedperson for four times. He has published more than 500 professional papers on domestic and international top-levelpublications. He was awarded the China Academy of Engineering: Guang Hua Engineering Science and Techno-

logy Prize (youth award), “The State Special Support Plan” National Millions of Talents Project, Science and Technology Awardfor Chinese Youth, and the Supervisor Award of the National Outstanding Doctoral Dissertations.

GAO Wei, et al. / Chin J Nat Med, 2020, 18(9): 641-642

– 642 –