Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• derivatives in microorganisms has been achieved by various teams. This article comprehensively reviews the research progress on the extraction, separation, pharmacological activity, biosynthesis, and synthetic biology of crocins. The biosynthesis of crocins is depicted in detail to shed light on the efficient

• clearance in vivo. Only a few plants can produce crocins, and the content of crocins in these plants is very low. Due to the numerous chiral centers, the total synthesis of crocins is challenging. Therefore, heterologous biosynthesis of crocins utilizing the synthetic biology strategy holds great potential

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• for the design of biosynthetic machineries to produce a variety of bioactive meroterpenoids. Keywords: αKG-dependent dioxygenases; enzyme engineering; fungal meroterpenoids; synthetic biology; terpene cyclases; Introduction Meroterpenoids are complex natural products with intricate skeletal

• acid, halogenated at C-3 (Figure 9). Today, with the improvement of gene synthesis and expression technologies, genes from a wide variety of species are available, further increasing the potential for applications of biogenetic resources. In the future, advances in synthetic biology will enable the

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• ligation from shorter 20 to 60 nt ODNs produced by automated de novo chemical synthesis. While these methods have made many projects in areas such as synthetic biology and protein engineering possible, they have various drawbacks. For example, they cannot produce genes and genomes with long repeats and

• . Keywords: automated synthesis; catching-by-polymerization; gene assembly; long oligonucleotide; synthetic biology; Introduction Long oligodeoxynucleotides (ODNs) are segments of DNAs extending beyond one hundred nucleotides (nt). Emerging research areas such as synthetic biology [1][2], protein

• synthesized ODNs of 20–60 nt in length using PCR or ligation [8]. While these methods have made possible the emergence of research areas such as synthetic biology [9][10][11][12][13][14], they have various drawbacks [3]. (1) Owing to the short length of the starting ODNs, a large number of them are needed in

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• , China, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China 10.3762/bjoc.18.144 Abstract Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in

• Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01Y036, China), Innovative and Research Teams Project of Guangdong Higher Education Institution (2021KCXTD001, China), Guangzhou Science and Technology Project (202102010114, China), and Shenzhen Institute of Synthetic

• Biology Scientific Research Program (DWKF20210002, China).

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• [7]. Hence, there is considerable interest in CYPs involved in triterpenoid and steroid metabolism in plants not only for improving our understanding of plant specialised metabolism, but also for synthetic biology and chemoenzymatic synthesis. In this review, we will provide an extensive overview of

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• categories of diterpenoid natural products with complicated polycyclic carbon skeletons and significant pharmacological activities. Despite exciting advances in organic chemistry, access to these skeletons is still highly challenging. Using synthetic biology to engineer microbes provides an innovative

• complexity [12]. Additionally, chemical transformations from commercial natural products are also tedious and currently limited to a few diterpene skeletons [8]. Engineering microbes via synthetic biology provides new opportunities to produce terpenoid carbon skeletons. All terpenoids are derived from the

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• chemistry and synthetic biology. Stereo- and regioselective hydroxylation at C9 (steroid numbering) is carried out using whole-cell biocatalysis, followed by the chemical cleavage of the C–C bond of the vicinal diol. The two-step method features mild reaction conditions and completely excludes the use of

• toxic oxidants. Keywords: chemoenzymatic synthesis; cortisol; hydroxylation; secosterol; whole-cell catalysis; Introduction Developments in the chemistry of steroids have stimulated extensive research interest in the exploration of new synthetic methods since the 1960s. Advances in synthetic biology

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• Information File 134: Data on acid–base transition and amide bond isomerism and NMR characterization of compounds 1–7. Funding The author would like to acknowledge Canadian federal government for funding the research chair for chemical synthetic biology (lead Dr. Budisa) at the University of Manitoba.

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• functional promiscuity of terpene biosynthetic pathways renders terpene biosynthesis susceptible to rational pathway engineering using the latest developments in the field of synthetic biology. These engineered pathways will not only facilitate the rational creation of both known and novel terpenoids, their

• . Keywords: bacterial sesquiterpenes and diterpenes; cytochrome P450; pathway engineering; synthetic biology; terpene biosynthesis; terpene cyclase; Introduction Evolutionary diversification of terpene biosynthetic pathways has resulted in the largest and most structurally diverse class of specialized

• synthetic biology to engineer pathways that will expand molecular diversity, especially around scaffolds associated with high-value compounds. The biosynthetic logic of terpene formation differs significantly from the logic employed by other classes of secondary metabolite biosynthetic pathways. Bacterial

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• linked with a bouquet of methods to broaden the platform of molecules with favourable olfactory properties. These include chemical synthesis, microbiology and molecular biology associated with biotechnology and combinations based on these methods. Hence also the most recent developments in synthetic

• biology will appear on the stage of the world of fragrances [40][41]. Terpene constituents 1–9 found in geranium and bergamot oils and specified odours of individual components. Perfumes are composed of compounds that are perceived immediately (top notes), that form the principal bouquet (heart notes) and

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• –protein interactions [19][20], CRISPR genome editing [21][22][23], DNA data storage [24][25], synthetic biology [26], bioconjugation [27] and others [28][29][30]. These applications frequently require modified ODNs that contain a wide variety of functional groups including those that cannot survive known

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• to build synthetic metabolism. Here I discuss the current challenges and limitations in synthetic metabolic engineering and elucidate how modern day enzymology can help to build a synthetic metabolism of the future. Keywords: enzymes; in vitro biochemistry; metabolic engineering; synthetic biology

• bottom-up might represent a valuable alternative strategy [6]. Linking enzymology and synthetic biology In summary, synthetic biology can develop its full potential, if it becomes able to harness the diversity of the millions of different enzyme variants and homologs that naturally exist. While such

• enzymatic data in a more standardized fashion. As a matter of fact, standardization has been an important driver in the development of synthetic biology. This is probably best demonstrated by the BioBrick System [62] and the multitude of standardized genetic elements that are available for the assembly of

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• Marcelo D. T. Torres Gislaine P. Andrade Roseli H. Sato Cibele N. Pedron Tania M. Manieri Giselle Cerchiaro Anderson O. Ribeiro Cesar de la Fuente-Nunez Vani X. Oliveira Jr. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil Synthetic Biology

• Group, MIT Synthetic Biology Center, Research Laboratory of Electronics, Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology; Broad Institute of MIT and Harvard, The Center for Microbiome Informatics and Therapeutics

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• needed that integrates the thorough appreciation of reaction rates in the design of chemical networks. Learning from the design principles applied in synthetic biology Genetic and small DNA-oligonucleotide networks provide an ideal test bed to address the basic principles of designing (bio)chemical

• reaction) were obtained. In stark contrast to the BZ reaction, however, the use of DNA or DNA-enzyme-based in vitro systems are amenable to rational design. Other approaches in synthetic biology use gene regulatory networks. Gene regulations provide both conceptual simplicity and modularity to design

• chemical approach, in contrast to synthetic biology, might involve the construction of a network of individual reactions that are well-characterized where the key kinetic parameters can all be experimentally verified. We recently showed that a chemical reaction network can be designed using enzymatic

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• -up synthetic-biology example of how this can be approached, see [55]. Challenge 2: finding conditions and mechanisms for minimal functional integration. A focused search for the specific experimental conditions and the set of molecular interaction mechanisms (physicochemical couplings) that lead to

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• life, we find in this book the misunderstandings –the most common ones– of what is today named “synthetic biology” as well as the beliefs spread by mass media, namely the mix-up of a program, the expression of the program, and the machine able to read and express the program (we consistently forget

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• structures by synthetic biology [6]. The aim of this review is to trace how our understanding of these feature of the biosynthesis has developed, and more specifically, the critical role that an array of chemical biology approaches [7] has played in furnishing the underlying data. These include, but are not

Sustainable catalysis

• Nicholas J. Turner

Beilstein J. Org. Chem. 2016, 12, 1778–1779, doi:10.3762/bjoc.12.167

• (EFPIA). CHEM21 is a large multi-group consortium organized into six different work-packages spanning various elements of green chemistry including biocatalysis, synthetic biology and non-precious metal catalysis. In addition, there are also work packages devoted to defining current and future targets

The role of alkyl substituents in deazaadenine-based diarylethene photoswitches

• Christopher Sarter,
• Michael Heimes and
• Andres Jäschke

Beilstein J. Org. Chem. 2016, 12, 1103–1110, doi:10.3762/bjoc.12.106

• DNA photoswitches for the application in bionanotechnology and synthetic biology. Keywords: diarylethene; nucleoside; electrocyclic rearrangement; photochromism; photoswitch; Introduction Most biomacromolecules are per se not responsive to light. Their conversion into photoresponsive molecules opens

• up new and innovative applications in materials sciences, bionanotechnology, synthetic biology, and biomedical diagnostics, and reversible photoswitching is a particularly attractive goal [1][2][3][4][5][6][7][8][9][10][11][12]. Light is a powerful and convenient trigger for manipulating structure

• important direction for the design of new efficient photoswitches for application in bionanotechnology and synthetic biology. Diarylethene photoswitches. A: classical design and photoisomerization reaction [27]. B: purine-based photoswitches (1st generation) [43][44], C: pyrimidine-based photoswitches (2nd

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• wealth of information that can be gained regarding the concentrations and flux of small molecules within these dynamic and complex environments. Additionally, the ability to fluorescently monitor targets such as small molecules inside of living cells could prove to be valuable for synthetic biology

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• [39]. Carboxysomal proteins have also been expressed in E. coli yielding a highly organised structure [41]. Use of carboxysomes for micro-compartmentalisation of CO2 biotransformation may therefore become a viable strategy in a range of synthetic biology applications, because not only CO2-transforming

• for specialised cofactors or maturation and folding processes. RuBisCO presents significant challenges for use in modular synthetic biology approaches, due to the observed inefficiency and requirement for expression of large amounts of protein. The difficulty of expression in hosts that do not

• naturally contain RuBisCO, such as E. coli, and the complicated nature of the heterologous RuBisCO systems currently developed in transgenic plants [80], means that the Calvin cycle is a challenging target for synthetic biology in non-photosynthetic microorganisms. Efforts focusing on increasing carbon

Is organic chemistry science – and does this question make any sense at all?

• Andreas Kirschning and
• Thomas A. C. Reydon

Beilstein J. Org. Chem. 2015, 11, 893–896, doi:10.3762/bjoc.11.100

• area of investigation [1][2][8]. In addition, this interest is linked to the rapidly emerging molecular bio- and life sciences and their impact on our societies and on the individual. The question what is “proper” science now is also debated in new areas of the biosciences, such as synthetic biology

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• information density of DNA, allow larger numbers of DNA fragments to autonomously self-assemble into large DNA constructs. This technology can therefore increase the size of DNA constructs that might be used in synthetic biology. Keywords: automated gene synthesis; artificially expanded genetic information

• systems; solid-phase DNA synthesis; synthetic biology; Introduction It has been nearly 50 years since the first solid-phase synthesis of DNA by Letsinger and Mahadevan [1][2]. This work laid the platform for new strategies in oligonucleotide synthesis, culminating in the development of phosphoramidite

• vision, now called “synthetic biology” [13][14][15][16][17], of converting automatically synthesized short DNA molecules (50–100 nucleotides in length) into much longer DNA constructs by autonomous self-assembly, without the cost of manual convergent assembly. In addition to the DARPA Foundries “1,000

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• development of "synthetic biology“ as a modern field over the past 30 years [1][2][3][4][5]. While oligonucleotides can be reliably prepared by automated synthesis up to ca. 100 nucleotides in length and (even today) are most often used as primers, many seek to create large DNA (L-DNA) constructs by assembly

• stranded DNA fragments “be limited to perhaps a dozen fragments at a time”. Fortunately, another development of synthetic biology offers an approach to mitigate these limitations of natural DNA as a matrix for autonomous self-assembly. This exploits a "second-generation" version of an artificially expanded