A roadmap to engineering antiviral natural products synthesis in microbes

Ma, Jingbo; Gu, Yang; Xu, Peng

doi:10.1016/j.copbio.2020.07.008

Cited by 26 publications

(24 citation statements)

References 67 publications

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“…However, some microorganisms can synthesize terpenoids ( Yamada et al, 2015 ). Furthermore, microbial strains can be engineered to produce such terpenoids that have antiviral activities ( Ma et al, 2020 ). The properties and medicinal uses of terpenoids are being continuously investigated by researchers for anticancer, antioxidant, antiviral, and anti-atherosclerotic activities ( Nazaruk and Borzym-Kluczyk, 2015 ).…”

Section: Microbial Metabolites As Potential Antiviral Candidatesmentioning

confidence: 99%

“…This class of metabolites can be produced in engineered fungi such Saccharomyces cerevisiae and Yarrowia. Lipolytica ( Ma et al, 2020 ). Oleanolic acid is such a terpenoid produced from genetically modified S. cerevisiae, which inhibited genome replication and transcription of HCV ( Zhao et al, 2018a ).…”

Section: Microbial Metabolites As Potential Antiviral Candidatesmentioning

confidence: 99%

“…Moreover, extraction of the natural products from the plants and the chemical synthesis of synthetic drugs have safety and economic concerns. Furthermore, conventional drugs become failed against viral infections and the onset of specific viral resistances against these drugs is a common phenomenon ( Linnakoski et al, 2018 ; Mulwa and Stadler, 2018 ; Ma et al, 2020 ). Therefore, researchers need to search for alternative source of safe and economically cost-effective antiviral natural products.…”

Section: Introductionmentioning

confidence: 99%

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Microbial Metabolites: The Emerging Hotspot of Antiviral Compounds as Potential Candidates to Avert Viral Pandemic Alike COVID-19

Raihan

Rabbee

Roy

et al. 2021

Front. Mol. Biosci.

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The present global COVID-19 pandemic caused by the noble pleomorphic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a vulnerable situation in the global healthcare and economy. In this pandemic situation, researchers all around the world are trying their level best to find suitable therapeutics from various sources to combat against the SARS-CoV-2. To date, numerous bioactive compounds from different sources have been tested to control many viral diseases. However, microbial metabolites are advantageous for drug development over metabolites from other sources. We herein retrieved and reviewed literatures from PubMed, Scopus and Google relevant to antiviral microbial metabolites by searching with the keywords “antiviral microbial metabolites,” “microbial metabolite against virus,” “microorganism with antiviral activity,” “antiviral medicine from microbial metabolite,” “antiviral bacterial metabolites,” “antiviral fungal metabolites,” “antiviral metabolites from microscopic algae’ and so on. For the same purpose, the keywords “microbial metabolites against COVID-19 and SARS-CoV-2” and “plant metabolites against COVID-19 and SARS-CoV-2” were used. Only the full text literatures available in English and pertinent to the topic have been included and those which are not available as full text in English and pertinent to antiviral or anti-SARS-CoV-2 activity were excluded. In this review, we have accumulated microbial metabolites that can be used as antiviral agents against a broad range of viruses including SARS-CoV-2. Based on this concept, we have included 330 antiviral microbial metabolites so far available to date in the data bases and were previously isolated from fungi, bacteria and microalgae. The microbial source, chemical nature, targeted viruses, mechanism of actions and IC50/EC50 values of these metabolites are discussed although mechanisms of actions of many of them are not yet elucidated. Among these antiviral microbial metabolites, some compounds might be very potential against many other viruses including coronaviruses. However, these potential microbial metabolites need further research to be developed as effective antiviral drugs. This paper may provide the scientific community with the possible secret of microbial metabolites that could be an effective source of novel antiviral drugs to fight against many viruses including SARS-CoV-2 as well as the future viral pandemics.

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Section: Microbial Metabolites As Potential Antiviral Candidatesmentioning

confidence: 99%

Section: Microbial Metabolites As Potential Antiviral Candidatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Microbial Metabolites: The Emerging Hotspot of Antiviral Compounds as Potential Candidates to Avert Viral Pandemic Alike COVID-19

Raihan

Rabbee

Roy

et al. 2021

Front. Mol. Biosci.

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“…It interacts with cyclophillins and blocks the conformational changes of the viral protein [ 24 , 25 ]. Many other natural antiviral agents have been identified and efforts to discover new bioactive metabolites, increase their efficacy and develop the most cost-effective methods of antiviral drug production are continuing [ 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Antiviral Cyanometabolites—A Review

et al. 2021

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Global processes, such as climate change, frequent and distant travelling and population growth, increase the risk of viral infection spread. Unfortunately, the number of effective and accessible medicines for the prevention and treatment of these infections is limited. Therefore, in recent years, efforts have been intensified to develop new antiviral medicines or vaccines. In this review article, the structure and activity of the most promising antiviral cyanobacterial products are presented. The antiviral cyanometabolites are mainly active against the human immunodeficiency virus (HIV) and other enveloped viruses such as herpes simplex virus (HSV), Ebola or the influenza viruses. The majority of the metabolites are classified as lectins, monomeric or dimeric proteins with unique amino acid sequences. They all show activity at the nanomolar range but differ in carbohydrate specificity and recognize a different epitope on high mannose oligosaccharides. The cyanobacterial lectins include cyanovirin-N (CV-N), scytovirin (SVN), microvirin (MVN), Microcystisviridis lectin (MVL), and Oscillatoria agardhii agglutinin (OAA). Cyanobacterial polysaccharides, peptides, and other metabolites also have potential to be used as antiviral drugs. The sulfated polysaccharide, calcium spirulan (CA-SP), inhibited infection by enveloped viruses, stimulated the immune system’s response, and showed antitumor activity. Microginins, the linear peptides, inhibit angiotensin-converting enzyme (ACE), therefore, their use in the treatment of COVID-19 patients with injury of the ACE2 expressing organs is considered. In addition, many cyanobacterial extracts were revealed to have antiviral activities, but the active agents have not been identified. This fact provides a good basis for further studies on the therapeutic potential of these microorganisms.

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“…Compared to plant-based production system, microbes have a number of advantages, including less dependence on arable land or climate changes, ease of genetic manipulation and large-scale production, as well as robust growth and high conversion rate across a wide range of low-cost renewable raw materials 6, 9 . Therefore, genetically modified microbes have been widely used to produce fuels, commodity chemicals and nutraceuticals 10 . With our increased knowledge of cellular physiology and understanding of molecular genetics toward higher and complex organisms, there is a growing interest to develop novel cellular chassis that may overcome the constraints of common host ( E. coli and S. cerevisiae ) 11 .…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of cannabinoid precursor olivetolic acid by overcoming rate-limiting steps in genetically engineered Yarrowia lipolytica

2021

Preprint

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Natural products acting on our central nervous systems are in utmost demand to fight against pain and mental disorders. Cannabinoids (CBDs) are proven neuroactive agents to treat anxiety, depression, chronic pain diseases, seizure, strokes and neurological disorders. The scarcity of the hemp-sourced CBD products and the prohibitive manufacturing cost limit the wide application of CBDs. Yeast metabolic engineering offers the flexibility to meet the ever-increasing market demand. In this work, we took a retrosynthetic approach and sequentially identified the rate-limiting steps to improve the biosynthesis of the CBD precursor olivetolic acid (OLA) in Yarrowia lipolytica. We debottlenecked the critical enzymatic steps to overcome the supply of hexanoyl-CoA, malonyl-CoA, acetyl-CoA, NADPH and ATPs to redirect carbon flux toward OLA. Implementation of these strategies led to an 83-fold increase in OLA titer in shaking flask experiment. This work may serve as a baseline for engineering CBD biosynthesis in oleaginous yeast species.

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A roadmap to engineering antiviral natural products synthesis in microbes

Abstract: Graphical abstract

Cited by 26 publications

References 67 publications

Microbial Metabolites: The Emerging Hotspot of Antiviral Compounds as Potential Candidates to Avert Viral Pandemic Alike COVID-19

Microbial Metabolites: The Emerging Hotspot of Antiviral Compounds as Potential Candidates to Avert Viral Pandemic Alike COVID-19

Antiviral Cyanometabolites—A Review

Biosynthesis of cannabinoid precursor olivetolic acid by overcoming rate-limiting steps in genetically engineered Yarrowia lipolytica

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