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Design in Synthetic Biology

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (1 August 2018) | Viewed by 46937

Special Issue Editors

Department of Chemistry, University of Nebraska-Lincoln, 634AA Hamilton Hall, Lincoln, NE, USA
Interests: synthetic biology; chemical biology; bioorganic chemistry; protein engineering; unnatural amino acid; genetic code; directed evolution; metabolic engineering
Department of Chemical & Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA
Interests: synthetic biology; metabolic engineering; protein engineering; codon expansion; systems biology

Special Issue Information

Dear Colleagues,

As a young multidisciplinary research field, Synthetic Biology has been enjoying rapid growth over recent years. It combines fundamental principles of science and engineering in order to achieve a precision design and an efficient construction of useful biological functions and systems. Synthetic Biology attracts interests from the fields of Biology, Chemistry, Mathematics, Chemical Engineering, Biomedical Engineering, Material Engineering, Computer Engineering, Electrical Engineering, etc. Applications of Synthetic Biology serve a very broad spectrum of goals, ranging from making basic scientific discoveries to solving practical problems, such as producing drugs and bio-based chemicals/fuels, improving traits of crops, and optimizing gene therapy.

The present Special Issue is aimed at bringing the most recent and exciting advances in Synthetic Biology to its audience. It covers, but is not limited to, new methods and novel applications in genetic circuit design, genetic code engineering, genome editing, DNA/genome synthesis, natural product discover/synthesis, novel pathway design/construction, metabolic engineering, biosensing, protein design/engineering, and mathematical modelling.

As Guest Editors, we cordially invite researchers to submit their recent advances in the field to this Special Issue of Molecules.

With best regards,

Dr. Jiantao Guo
Dr. Wei Niu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Synthetic Biology
  • Chemical Biology
  • Natural Product Biosynthesis
  • Protein Engineering
  • Genetic Code
  • Metabolic Engineering
  • Biocatalysis

Published Papers (8 papers)

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Research

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13 pages, 2459 KiB  
Article
Improved l-Leucine Production in Corynebacterium glutamicum by Optimizing the Aminotransferases
by Li-Yan Feng, Jian-Zhong Xu and Wei-Guo Zhang
Molecules 2018, 23(9), 2102; https://doi.org/10.3390/molecules23092102 - 21 Aug 2018
Cited by 19 | Viewed by 4980
Abstract
The production of branched-chain amino acids (BCAAs) is still challenging, therefore we rationally engineered Corynebacterium glutamicum FA-1 to increase the l-leucine production by optimizing the aminotransferases. Based on this, we investigated the effects of the native aminotransferases, i.e., branched-chain amino acid aminotransferase [...] Read more.
The production of branched-chain amino acids (BCAAs) is still challenging, therefore we rationally engineered Corynebacterium glutamicum FA-1 to increase the l-leucine production by optimizing the aminotransferases. Based on this, we investigated the effects of the native aminotransferases, i.e., branched-chain amino acid aminotransferase (BCAT; encoded by ilvE) and aspartate aminotransferase (AspB; encoded by aspB) on l-leucine production in C. glutamicum. The strain FA-1△ilvE still exhibited significant growth without leucine addition, while FA-1△ilvEaspB couldn’t, which indicated that AspB also contributes to L-leucine synthesis in vivo and the yield of leucine reached 20.81 ± 0.02 g/L. It is the first time that AspB has been characterized for l-leucine synthesis activity. Subsequently, the aromatic aminotransferase TyrB and the putative aspartate aminotransferases, the aspC, yhdR, ywfG gene products, were cloned, expressed and characterized for leucine synthesis activity in FA-1△ilvEaspB. Only TyrB was able to synthesize l-leucine and the l-leucine production was 18.55 ± 0.42 g/L. The two putative branched-chain aminotransferase genes, ybgE and CaIlvE, were also cloned and expressed. Both genes products function efficiently in BCAAs biosynthesis. This is the first report of a rational modification of aminotransferase activity that improves the l-leucine production through optimizing the aminotransferases. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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13 pages, 2260 KiB  
Article
(2E,5E)-2,5-Bis(3-hydroxy-4-methoxybenzylidene) cyclopentanone Exerts Anti-Melanogenesis and Anti-Wrinkle Activities in B16F10 Melanoma and Hs27 Fibroblast Cells
by Hee Jin Jung, A Kyoung Lee, Yeo Jin Park, Sanggwon Lee, Dongwan Kang, Young Suk Jung, Hae Young Chung and Hyung Ryong Moon
Molecules 2018, 23(6), 1415; https://doi.org/10.3390/molecules23061415 - 11 Jun 2018
Cited by 16 | Viewed by 4716
Abstract
Ultraviolet (UV) radiation exposure is the primary cause of extrinsic skin aging, which results in skin hyperpigmentation and wrinkling. In this study, we investigated the whitening effect of (2E,5E)-2,5-bis(3-hydroxy-4-methoxybenzylidene)cyclopentanone (BHCP) on B16F10 melanoma and its anti-wrinkle activity on Hs27 [...] Read more.
Ultraviolet (UV) radiation exposure is the primary cause of extrinsic skin aging, which results in skin hyperpigmentation and wrinkling. In this study, we investigated the whitening effect of (2E,5E)-2,5-bis(3-hydroxy-4-methoxybenzylidene)cyclopentanone (BHCP) on B16F10 melanoma and its anti-wrinkle activity on Hs27 fibroblasts cells. BHCP was found to potently inhibit tyrosinase, with 50% inhibition concentration (IC50) values of 1.10 µM and 8.18 µM for monophenolase (l-tyrosine) and diphenolase (l-DOPA), and the enzyme kinetics study revealed that BHCP is a competitive-type tyrosinase inhibitor. Furthermore, BHCP significantly inhibited melanin content and cellular tyrosinase activity, and downregulated the levels of microphthalmia-associated transcription factor (MITF), phosphorylated levels of cAMP response element-binding (CREB) protein, and tyrosinase in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells. Moreover, BHCP inhibited the phosphorylation of p65 and expression of matrix metalloproteinases (MMP-1, MMP-9, MMP-12, and MMP-13) in Hs27 fibroblasts stimulated with UV radiation. Therefore, our results demonstrate that BHCP may be a good candidate for the development of therapeutic agents for diseases associated with hyperpigmentation and wrinkling. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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15 pages, 4794 KiB  
Article
Functional Characterisation of New Sesquiterpene Synthase from the Malaysian Herbal Plant, Polygonum Minus
by Nor Azizun Rusdi, Hoe-Han Goh, Suriana Sabri, Ahmad Bazli Ramzi, Normah Mohd Noor and Syarul Nataqain Baharum
Molecules 2018, 23(6), 1370; https://doi.org/10.3390/molecules23061370 - 06 Jun 2018
Cited by 14 | Viewed by 4985
Abstract
Polygonum minus (syn. Persicaria minor) is a herbal plant that is well known for producing sesquiterpenes, which contribute to its flavour and fragrance. This study describes the cloning and functional characterisation of PmSTPS1 and PmSTPS2, two sesquiterpene synthase genes that [...] Read more.
Polygonum minus (syn. Persicaria minor) is a herbal plant that is well known for producing sesquiterpenes, which contribute to its flavour and fragrance. This study describes the cloning and functional characterisation of PmSTPS1 and PmSTPS2, two sesquiterpene synthase genes that were identified from P. minus transcriptome data mining. The full-length sequences of the PmSTPS1 and PmSTPS2 genes were expressed in the E. coli pQE-2 expression vector. The sizes of PmSTPS1 and PmSTPS2 were 1098 bp and 1967 bp, respectively, with open reading frames (ORF) of 1047 and 1695 bp and encoding polypeptides of 348 and 564 amino acids, respectively. The proteins consist of three conserved motifs, namely, Asp-rich substrate binding (DDxxD), metal binding residues (NSE/DTE), and cytoplasmic ER retention (RxR), as well as the terpene synthase family N-terminal domain and C-terminal metal-binding domain. From the in vitro enzyme assays, using the farnesyl pyrophosphate (FPP) substrate, the PmSTPS1 enzyme produced multiple acyclic sesquiterpenes of β-farnesene, α-farnesene, and farnesol, while the PmSTPS2 enzyme produced an additional nerolidol as a final product. The results confirmed the roles of PmSTPS1 and PmSTPS2 in the biosynthesis pathway of P. minus, to produce aromatic sesquiterpenes. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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16 pages, 3751 KiB  
Article
Replacing Standard Reporters from Molecular Cloning Plasmids with Chromoproteins for Positive Clone Selection
by Margarita Daniela Tafoya-Ramírez, Felipe Padilla-Vaca, Ana Patricia Ramírez-Saldaña, Josué Daniel Mora-Garduño, Ángeles Rangel-Serrano, Naurú Idalia Vargas-Maya, Luz Janeth Herrera-Gutiérrez and Bernardo Franco
Molecules 2018, 23(6), 1328; https://doi.org/10.3390/molecules23061328 - 31 May 2018
Cited by 7 | Viewed by 7270
Abstract
Cloning and expression plasmids are the workhorses of modern molecular biology. Despite the pathway paved by synthetic biology, laboratories around the globe still relay on standard cloning techniques using plasmids with reporter proteins for positive clone selection, such as β-galactosidase alpha peptide complementation [...] Read more.
Cloning and expression plasmids are the workhorses of modern molecular biology. Despite the pathway paved by synthetic biology, laboratories around the globe still relay on standard cloning techniques using plasmids with reporter proteins for positive clone selection, such as β-galactosidase alpha peptide complementation for blue/white screening or ccdB, which encodes for a toxic DNA gyrase. These reporters, when interrupted, serve as a positive clone detection system. In the present report, we show that molecular cloning plasmids bearing the coding sequence for a 25.4 kDa protein, AmilCP, encoded by a 685 bp gene, that is well expressed in Escherichia coli, render blue-purple colonies. Using this reporter protein, we developed and tested a cloning system based on the constitutive expression of the non-toxic AmilCP protein, that once interrupted, the loss of purple color serves to facilitate positive clone selection. The main advantage of this system is that is less expensive than other systems since media do not contain chromogenic markers such as X-gal, which is both expensive and cumbersome to prepare and use, or inductors such as IPTG. We also designed an inducible expression plasmid suitable for recombinant protein expression that also contains AmilCP cloning selection marker, a feature not commonly found in protein expression plasmids. The use of chromogenic reporters opens an important avenue for its application in other organisms besides E. coli for clone selection or even for mutant selection. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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15 pages, 6066 KiB  
Article
Multicomponent Domino Synthesis, Anticancer Activity and Molecular Modeling Simulation of Complex Dispirooxindolopyrrolidines
by Natarajan Arumugam, Abdulrahman I. Almansour, Raju Suresh Kumar, Periyasami Govindasami, Dhaifallah M. Al-thamili, Rajapandian Krishnamoorthy, Vaiyapuri Subbarayan Periasamy, Ali A. Alshatwi, S. M. Mahalingam, Shankar Thangamani and J. Carlos Menéndez
Molecules 2018, 23(5), 1094; https://doi.org/10.3390/molecules23051094 - 05 May 2018
Cited by 12 | Viewed by 3978
Abstract
A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus [...] Read more.
A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5am led to their apoptotic cell death. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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4590 KiB  
Article
Biochemical, Physiological and Transcriptomic Comparison between Burley and Flue-Cured Tobacco Seedlings in Relation to Carbohydrates and Nitrate Content
by Yafei Li, Huijuan Yang, Dong Chang, Shuzhen Lin, Yuqing Feng, Jingjing Li and Hongzhi Shi
Molecules 2017, 22(12), 2126; https://doi.org/10.3390/molecules22122126 - 02 Dec 2017
Cited by 22 | Viewed by 4666
Abstract
Burley tobacco is a genotype of chloroplast-deficient mutant with accumulates high levels of tobacco-specific nitrosamines (TSNAs) which would induce malignant tumors in animals. Nitrate is a principle precursor of tobacco-specific nitrosamines. Nitrate content in burley tobacco was significantly higher than that in flue-cured [...] Read more.
Burley tobacco is a genotype of chloroplast-deficient mutant with accumulates high levels of tobacco-specific nitrosamines (TSNAs) which would induce malignant tumors in animals. Nitrate is a principle precursor of tobacco-specific nitrosamines. Nitrate content in burley tobacco was significantly higher than that in flue-cured tobacco. The present study investigated differences between the two tobacco types to explore the mechanisms of nitrate accumulation in burley tobacco. transcripts (3079) related to the nitrogen and carbon metabolism were observed. Expression of genes involved in carbon fixation, glucose and starch biosynthesis, nitrate translocation and assimilation were significantly low in burley tobacco than flue-cured tobacco. Being relative to flue-cured tobacco, burley tobacco was significantly lower at total nitrogen and carbohydrate content, nitrate reductase and glutamine synthetase activities, chlorophyll content and photosynthetic rate (Pn), but higher nitrate content. Burley tobacco required six-fold more nitrogen fertilizers than flue-cured tobacco, but both tobaccos had a similar leaf biomass. Reduced chlorophyll content and photosynthetic rate (Pn) might result in low carbohydrate formation, and low capacity of nitrogen assimilation and translocation might lead to nitrate accumulation in burley tobacco. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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Review

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19 pages, 2785 KiB  
Review
Recent Development of Genetic Code Expansion for Posttranslational Modification Studies
by Hao Chen, Sumana Venkat, Paige McGuire, Qinglei Gan and Chenguang Fan
Molecules 2018, 23(7), 1662; https://doi.org/10.3390/molecules23071662 - 08 Jul 2018
Cited by 33 | Viewed by 6342
Abstract
Nowadays advanced mass spectrometry techniques make the identification of protein posttranslational modifications (PTMs) much easier than ever before. A series of proteomic studies have demonstrated that large numbers of proteins in cells are modified by phosphorylation, acetylation and many other types of PTMs. [...] Read more.
Nowadays advanced mass spectrometry techniques make the identification of protein posttranslational modifications (PTMs) much easier than ever before. A series of proteomic studies have demonstrated that large numbers of proteins in cells are modified by phosphorylation, acetylation and many other types of PTMs. However, only limited studies have been performed to validate or characterize those identified modification targets, mostly because PTMs are very dynamic, undergoing large changes in different growth stages or conditions. To overcome this issue, the genetic code expansion strategy has been introduced into PTM studies to genetically incorporate modified amino acids directly into desired positions of target proteins. Without using modifying enzymes, the genetic code expansion strategy could generate homogeneously modified proteins, thus providing powerful tools for PTM studies. In this review, we summarized recent development of genetic code expansion in PTM studies for research groups in this field. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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48 pages, 21275 KiB  
Review
Application of the Asymmetric Pictet–Spengler Reaction in the Total Synthesis of Natural Products and Relevant Biologically Active Compounds
by Majid M. Heravi, Vahideh Zadsirjan and Masumeh Malmir
Molecules 2018, 23(4), 943; https://doi.org/10.3390/molecules23040943 - 18 Apr 2018
Cited by 44 | Viewed by 9439
Abstract
Tetrahydroisoquinolines are the framework of numerous natural products predominantly alkaloids, an important and one of the most wide spread families of naturally occurring compounds in the plant kingdom. Tetrahydroisoquinolines are commonly constructed through an old reaction, the so-called Pictet–Spengler Reaction (PSR). In this [...] Read more.
Tetrahydroisoquinolines are the framework of numerous natural products predominantly alkaloids, an important and one of the most wide spread families of naturally occurring compounds in the plant kingdom. Tetrahydroisoquinolines are commonly constructed through an old reaction, the so-called Pictet–Spengler Reaction (PSR). In this reaction, a β-aryl ethylamine undergoes an acid mediated condensation with a suitable aldehyde or ketone, followed by ring closure. In this review, we aim to highlight the applications of the asymmetric variant of this old name reaction in the total synthesis of natural products, chiefly, alkaloids, which exhibit significant biological properties. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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