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Biology
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Bio-Based Chemicals Biosynthesis and Metabolic Regulation
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Bio-Based Chemicals Biosynthesis and Metabolic Regulation

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Biotechnology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 15774

Special Issue Editors

Prof. Dr. Tingyi Wen

E-Mail Website
Guest Editor
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Interests: industrial microbiology; metabolic engineering; genetic engineering; genome editing; gene expression and regulation; amino acids and derivatives; biological fermentation
Dr. Yun Zhang

E-Mail Website
Guest Editor
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Interests: biotechnology; molecular biology; genome-scale metabolic model; proteomics; genetic modification; microbial cell factory; fermentation

Special Issue Information

Dear Colleagues,

Environmentally friendly microbial processes are capable of converting renewable biomass resources into bulk chemicals fulfilled by the design and construction of microbial cell factories, which provides sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. In the last decade, major advances have been made in pathway design and metabolic regulation to drive more carbon flux towards the synthesis of non-natural or natural products of industrial interest in microbial cells.

Microbial cellular metabolism is tightly controlled by intricate regulatory mechanisms at the different system levels, and is strictly regulated to ensure the dynamic adaptation of biochemical reaction fluxes for maintaining cell homeostasis, to eventually achieve optimal metabolic fitness. This has increased the demand for understanding cellular metabolism and characterizing cell phenotypes. A key issue in bio-manufacturing patterns is to maximize the carbon yield from the substrates to the target product; however, this is difficult to achieve due to the competition or conflict between cell growth and bioproduction. Metabolic reprogramming in microbial cells has been pursued by taking advantage of metabolic engineering, genetic transformation, and biotechnologies, including genome editing, sensor-regulator-based and quorum-sensing circuit-based dynamic control systems, to overcome the metabolic bottleneck in product synthesis for the improvement of production rate and yield.

In this Special Issue, we hope to provide an extensive exploration of industrial microorganism and biotechnology for bio-based chemical biosynthesis. The scopes of this Special Issue include the directed modulation of metabolic networks or the improvement of cellular properties for chemical overproduction, the construction of microbial cell factories for non-natural product biosynthesis or recombinant protein production and biological transformation of industrial interest. Papers describing new genome editing methods or dynamic regulation systems for converting microorganisms into microbial cell factories and other aspects of genetic transformation for strain improvement are also welcome. We aim to publish papers in this Special Issue that represent important advances of significance to specialists within industrial microorganism and biotechnology fields.

Prof. Dr. Tingyi Wen
Dr. Yun Zhang
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. Biology is an international peer-reviewed open access monthly 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

  • bio-based chemicals biosynthesis
  • metabolic engineering
  • genetic transformation
  • metabolic regulation
  • genome editing
  • fermentation
  • whole-cell catalysis

Published Papers (5 papers)

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Research

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17 pages, 3256 KiB  
Article
Model-Guided Metabolic Rewiring for Gamma-Aminobutyric Acid and Butyrolactam Biosynthesis in Corynebacterium glutamicum ATCC13032
by Yun Zhang, Jing Zhao, Xueliang Wang, Yuan Tang, Shuwen Liu and Tingyi Wen
Biology 2022, 11(6), 846; https://doi.org/10.3390/biology11060846 - 31 May 2022
Cited by 6 | Viewed by 2451
Abstract
Gamma-aminobutyric acid (GABA) can be used as a bioactive component in the pharmaceutical industry and a precursor for the synthesis of butyrolactam, which functions as a monomer for the synthesis of polyamide 4 (nylon 4) with improved thermal stability and high biodegradability. The [...] Read more.
Gamma-aminobutyric acid (GABA) can be used as a bioactive component in the pharmaceutical industry and a precursor for the synthesis of butyrolactam, which functions as a monomer for the synthesis of polyamide 4 (nylon 4) with improved thermal stability and high biodegradability. The bio-based fermentation production of chemicals using microbes as a cell factory provides an alternative to replace petrochemical-based processes. Here, we performed model-guided metabolic engineering of Corynebacterium glutamicum for GABA and butyrolactam fermentation. A GABA biosynthetic pathway was constructed using a bi-cistronic expression cassette containing mutant glutamate decarboxylase. An in silico simulation showed that the increase in the flux from acetyl-CoA to α-ketoglutarate and the decrease in the flux from α-ketoglutarate to succinate drove more flux toward GABA biosynthesis. The TCA cycle was reconstructed by increasing the expression of acn and icd genes and deleting the sucCD gene. Blocking GABA catabolism and rewiring the transport system of GABA further improved GABA production. An acetyl-CoA-dependent pathway for in vivo butyrolactam biosynthesis was constructed by overexpressing act-encoding ß-alanine CoA transferase. In fed-batch fermentation, the engineered strains produced 23.07 g/L of GABA with a yield of 0.52 mol/mol from glucose and 4.58 g/L of butyrolactam. The metabolic engineering strategies can be used for genetic modification of industrial strains to produce target chemicals from α-ketoglutarate as a precursor, and the engineered strains will be useful to synthesize the bio-based monomer of polyamide 4 from renewable resources. Full article
(This article belongs to the Special Issue Bio-Based Chemicals Biosynthesis and Metabolic Regulation)
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12 pages, 2461 KiB  
Article
Novel Glycosylation by Amylosucrase to Produce Glycoside Anomers
by Jiumn-Yih Wu, Hsiou-Yu Ding, Shun-Yuan Luo, Tzi-Yuan Wang, Yu-Li Tsai and Te-Sheng Chang
Biology 2022, 11(6), 822; https://doi.org/10.3390/biology11060822 - 27 May 2022
Cited by 2 | Viewed by 2154
Abstract
Glycosylation occurring at either lipids, proteins, or sugars plays important roles in many biological systems. In nature, enzymatic glycosylation is the formation of a glycosidic bond between the anomeric carbon of the donor sugar and the functional group of the sugar acceptor. This [...] Read more.
Glycosylation occurring at either lipids, proteins, or sugars plays important roles in many biological systems. In nature, enzymatic glycosylation is the formation of a glycosidic bond between the anomeric carbon of the donor sugar and the functional group of the sugar acceptor. This study found novel glycoside anomers without an anomeric carbon linkage of the sugar donor. A glycoside hydrolase (GH) enzyme, amylosucrase from Deinococcus geothermalis (DgAS), was evaluated to glycosylate ganoderic acid F (GAF), a lanostane triterpenoid from medicinal fungus Ganoderma lucidum, at different pH levels. The results showed that GAF was glycosylated by DgAS at acidic conditions pH 5 and pH 6, whereas the activity dramatically decreased to be undetectable at pH 7 or pH 8. The biotransformation product was purified by preparative high-performance liquid chromatography and identified as unusual α-glucosyl-(2→26)-GAF and β-glucosyl-(2→26)-GAF anomers by mass and nucleic magnetic resonance (NMR) spectroscopy. We further used DgAS to catalyze another six triterpenoids. Under the acidic conditions, two of six compounds, ganoderic acid A (GAA) and ganoderic acid G (GAG), could be converted to α–glucosyl-(2→26)-GAA and β–glucosyl-(2→26)-GAA anomers and α-glucosyl-(2→26)-GAG and β-glucosyl-(2→26)-GAG anomers, respectively. The glycosylation of triterpenoid aglycones was first confirmed to be converted via a GH enzyme, DgAS. The novel enzymatic glycosylation-formed glycoside anomers opens a new bioreaction in the pharmaceutical industry and in the biotechnology sector. Full article
(This article belongs to the Special Issue Bio-Based Chemicals Biosynthesis and Metabolic Regulation)
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20 pages, 3806 KiB  
Article
l-Serine Biosensor-Controlled Fermentative Production of l-Tryptophan Derivatives by Corynebacterium glutamicum
by Lenny Ferrer, Mahmoud Elsaraf, Melanie Mindt and Volker F. Wendisch
Biology 2022, 11(5), 744; https://doi.org/10.3390/biology11050744 - 13 May 2022
Cited by 8 | Viewed by 3427
Abstract
l-Tryptophan derivatives, such as hydroxylated or halogenated l-tryptophans, are used in therapeutic peptides and agrochemicals and as precursors of bioactive compounds, such as serotonin. l-Tryptophan biosynthesis depends on another proteinogenic amino acid, l-serine, which is condensed with indole-3-glycerophosphate by [...] Read more.
l-Tryptophan derivatives, such as hydroxylated or halogenated l-tryptophans, are used in therapeutic peptides and agrochemicals and as precursors of bioactive compounds, such as serotonin. l-Tryptophan biosynthesis depends on another proteinogenic amino acid, l-serine, which is condensed with indole-3-glycerophosphate by tryptophan synthase. This enzyme is composed of the α-subunit TrpA, which catalyzes the retro-aldol cleavage of indole-3-glycerol phosphate, yielding glyceraldehyde-3-phosphate and indole, and the β-subunit TrpB that catalyzes the β-substitution reaction between indole and l-serine to water and l-tryptophan. TrpA is reported as an allosteric actuator, and its absence severely attenuates TrpB activity. In this study, however, we showed that Corynebacterium glutamicum TrpB is catalytically active in the absence of TrpA. Overexpression of C. glutamicumtrpB in a trpBA double deletion mutant supported growth in minimal medium only when exogenously added indole was taken up into the cell and condensed with intracellularly synthesized l-serine. The fluorescence reporter gene of an l-serine biosensor, which was based on the endogenous transcriptional activator SerR and its target promoter PserE, was replaced by trpB. This allowed for l-serine-dependent expression of trpB in an l-serine-producing strain lacking TrpA. Upon feeding of the respective indole derivatives, this strain produced the l-tryptophan derivatives 5-hydroxytryptophan, 7-bromotryptophan, and 5-fluorotryptophan. Full article
(This article belongs to the Special Issue Bio-Based Chemicals Biosynthesis and Metabolic Regulation)
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16 pages, 9502 KiB  
Article
Transcriptome Profiling Reveals Differential Gene Expression of Laccase Genes in Aspergillus terreus KC462061 during Biodegradation of Crude Oil
by Nada K. Alharbi, Mayasar I. Alzaban, Fawziah M. Albarakaty, Abeer R. M. Abd El-Aziz, Ahlam H. AlRokban and Mohamed A. Mahmoud
Biology 2022, 11(4), 564; https://doi.org/10.3390/biology11040564 - 7 Apr 2022
Cited by 3 | Viewed by 1814
Abstract
Fungal laccases have high catalytic efficiency and are utilized for the removal of crude oil because they oxidize various aliphatic and aromatic hydrocarbons and convert them into harmless compounds or less toxic compounds, thus accelerating the biodegradation potential of crude oil. Laccases are [...] Read more.
Fungal laccases have high catalytic efficiency and are utilized for the removal of crude oil because they oxidize various aliphatic and aromatic hydrocarbons and convert them into harmless compounds or less toxic compounds, thus accelerating the biodegradation potential of crude oil. Laccases are important gene families and the function of laccases genes varied widely based on transcription and function. Biodegradation of crude oil using Aspergillus terreus KC462061 was studied in the current study beside the transcription level of eight laccase (Lcc) genes have participated in biodegradation in the presence of aromatic compounds, and metal ions. Time-course profiles of laccase activity in the presence of crude oil indicated that the five inducers individual or combined have a very positive on laccase activity. In the status of the existence of crude oil, the synergistic effect of Cu-ABTS compound caused an increase in laccase yields up to 22-fold after 10 days than control. The biodegradation efficiencies of A. terreus KC462061 for aliphatic and aromatic hydrocarbons of crude oil were 82.1 ± 0.2% and 77.4 ± 0.6%, respectively. The crude oil biodegradation efficiency was improved by the supplemented Cu-ABTS compound in A. terreus KC462061. Gas chromatography–mass spectrometry was a very accurate tool to demonstrate the biodegradation efficiencies of A. terreus KC462061 for crude oil. Significant differences were observed in the SDS-PAGE of A. terreus KC462061 band intensities of laccase proteins after the addition of five inducers, but the Cu-ABTS compound highly affects very particular laccase electrophoresis. Quantitative real-time polymerase chain reaction (qPCR) was used for the analysis of transcription profile of eight laccase genes in A. terreus KC462061 with a verified reference gene. Cu2+ ions and Cu-ABTS were highly effective for efficient laccase expression profiling, mainly via Lcc11 and 12 transcription induction. The current study will explain the theoretical foundation for laccase transcription in A. terreus KC462061, paving the road for commercialization and usage. Full article
(This article belongs to the Special Issue Bio-Based Chemicals Biosynthesis and Metabolic Regulation)
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Review

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33 pages, 3428 KiB  
Review
CRISPR-Mediated Base Editing: From Precise Point Mutation to Genome-Wide Engineering in Nonmodel Microbes
by Mengyuan Li, Yi-Xin Huo and Shuyuan Guo
Biology 2022, 11(4), 571; https://doi.org/10.3390/biology11040571 - 9 Apr 2022
Cited by 6 | Viewed by 5329
Abstract
Nonmodel microbes with unique and diverse metabolisms have become rising stars in synthetic biology; however, the lack of efficient gene engineering techniques still hinders their development. Recently, the use of base editors has emerged as a versatile method for gene engineering in a [...] Read more.
Nonmodel microbes with unique and diverse metabolisms have become rising stars in synthetic biology; however, the lack of efficient gene engineering techniques still hinders their development. Recently, the use of base editors has emerged as a versatile method for gene engineering in a wide range of organisms including nonmodel microbes. This method is a fusion of impaired CRISPR/Cas9 nuclease and base deaminase, enabling the precise point mutation at the target without inducing homologous recombination. This review updates the latest advancement of base editors in microbes, including the conclusion of all microbes that have been researched by base editors, the introduction of newly developed base editors, and their applications. We provide a list that comprehensively concludes specific applications of BEs in nonmodel microbes, which play important roles in industrial, agricultural, and clinical fields. We also present some microbes in which BEs have not been fully established, in the hope that they are explored further and so that other microbial species can achieve arbitrary base conversions. The current obstacles facing BEs and solutions are put forward. Lastly, the highly efficient BEs and other developed versions for genome-wide reprogramming of cells are discussed, showing great potential for future engineering of nonmodel microbes. Full article
(This article belongs to the Special Issue Bio-Based Chemicals Biosynthesis and Metabolic Regulation)
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