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Biomanufacturing of Natural Bioactive Compounds
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Biomanufacturing of Natural Bioactive Compounds

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 11563

Special Issue Editor

Dr. Honglei Liu

E-Mail Website
Guest Editor
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
Interests: bioactive compounds; sulfur metabolism; biosynthesis; podophylotoxin

Special Issue Information

Dear Colleagues,

Natural bioactive compounds are natural products with pharmacological activity produced by animal, plants, and microorganisms, such as podophyllotoxin, paclitaxel, and (-)-β-elemene. These compounds are commonly secondary metabolic products with complex structures and low yields, which make it difficult to obtain them as well as synthesize them chemically.

Biosynthesis, with the use enzymatic reactions, shows prominent advantage in the synthesis of natural bioactive products. Using cell factory or engineering enzyme to synthesize and catalyze the production of highly active natural products has broad prospects. The cellular uptake of special substrates, biosynthesis using enzymatic reactions with cloned gene (clusters) to improve yields or activity, and improved final products extraction methods are widely studied by many groups.

This Special Issue aims to provide a broad overview of the biosynthesis of natural bioactive compounds. Original research articles or reviews that discuss the transport of complicated substrates, expression of related genes, biosynthesis from simple substrate or derivation from prodrugs, and improved extraction methodologies of natural bioactive compounds as well as other related articles are welcome.

Dr. Honglei Liu
Guest Editor

Manuscript Submission Information

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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

  • bioactive compounds
  • natural products
  • biosynthesis
  • derivation
  • cell factory

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Published Papers (7 papers)

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Research

Jump to: Review

12 pages, 1606 KiB  
Article
The Effects of Different Thiol-Containing Compounds on the Degradation of Sulforaphene
by Rui Gao, Pingxiang Liu, Jingxiu Bi, Yuying Jiang, Tong Zhao, Xuexia Yuan, Chao Zhang and Yutao Wang
Molecules 2024, 29(18), 4328; https://doi.org/10.3390/molecules29184328 - 12 Sep 2024
Viewed by 499
Abstract
Sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), produced by myrosinase hydrolysis of glucoraphenin (4-methylsulfinyl-3-butenyl glucosinolate) found in radish seeds, is strongly associated with cancer prevention. In this study, we investigated the stability of SFE (purity above 98%) under various thiol-containing compounds at 25 °C, such as [...] Read more.
Sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), produced by myrosinase hydrolysis of glucoraphenin (4-methylsulfinyl-3-butenyl glucosinolate) found in radish seeds, is strongly associated with cancer prevention. In this study, we investigated the stability of SFE (purity above 98%) under various thiol-containing compounds at 25 °C, such as sodium hydrosulfide (NaHS), glutathione (GSH), and cysteine (Cys). We observed that the degradation of SFE was closely related to the presence and dissociation capacity of thiol-containing compounds in the solution, particularly the thiol group. We found that the degradation rate of SFE was influenced by incubation with NaHS, GSH, and Cys, with distinct degradation products detected for each of these thiol-containing compounds. Compared to GSH, sulfide and Cys played important roles in promoting the degradation of SFE. Furthermore, we found substantial quantities of hydrogen sulfide in conjunction with SFE during the hydrolysis process of seeds, and a heat treatment of the seeds resulted in increased production of SFE. However, the introduction of sulfide-oxidizing bacteria to the hydrolytic system did not exhibit any inhibitory effect on the degradation of SFE. These results provided a guideline for industries to improve the stability of SFE during preparation. Full article
(This article belongs to the Special Issue Biomanufacturing of Natural Bioactive Compounds)
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17 pages, 2273 KiB  
Article
Metabolomic Analysis of Carotenoids Biosynthesis by Sphingopyxis sp. USTB-05
by Chao Liu, Qianqian Xu, Yang Liu, Meijie Song, Xiaoyu Cao, Xinyue Du and Hai Yan
Molecules 2024, 29(17), 4235; https://doi.org/10.3390/molecules29174235 - 6 Sep 2024
Viewed by 802
Abstract
Carotenoids belonging to the class of tetraterpenoids have extensive applications in medicine, food, nutrition, cosmetics, and feed. Among them, lutein and zeaxanthin can prevent macular degeneration in the elderly, which is very important for protecting vision. Here, we introduce the first metabolomic analysis [...] Read more.
Carotenoids belonging to the class of tetraterpenoids have extensive applications in medicine, food, nutrition, cosmetics, and feed. Among them, lutein and zeaxanthin can prevent macular degeneration in the elderly, which is very important for protecting vision. Here, we introduce the first metabolomic analysis of Sphingopyxis sp. USTB-05, aiming to shed light on the biosynthesis of carotenoids. Sphingopyxis sp. USTB-05 has the complete methylerythritol 4-phosphate (MEP) pathway and carotenoid biosynthesis pathway, especially involved in the bioconversion of zeaxanthin, violaxanthin, and astaxanthin. Metabolomic profiling identified seven carotenes and six xanthophylls synthesized by Sphingopyxis sp. USTB-05. Zeaxanthin, in particular, was found to be the most abundant, with a content of 37.1 µg/g dry cells. Collectively, the results presented herein greatly enhance our understanding of Sphingopyxis sp. USTB-05 in carotenoids biosynthesis, and thus further accelerate its fundamental molecular investigations and biotechnological applications. Full article
(This article belongs to the Special Issue Biomanufacturing of Natural Bioactive Compounds)
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23 pages, 1786 KiB  
Article
UHPLC-HRMS/MS Chemical Fingerprinting of the Bioactive Partition from Cultivated Piper aduncum L.
by Adélia Viviane de Luna, Thayssa da Silva Ferreira Fagundes, Ygor Jessé Ramos, Marlon Heggdorne de Araújo, Michelle Frazão Muzitano, Sanderson Dias Calixto, Thatiana Lopes Biá Ventura Simão, George Azevedo de Queiroz, Elsie Franklin Guimarães, André Mesquita Marques and Davyson de Lima Moreira
Molecules 2024, 29(8), 1690; https://doi.org/10.3390/molecules29081690 - 9 Apr 2024
Viewed by 1953
Abstract
Piper aduncum L. is widely distributed in tropical regions and the ethnobotanical uses of this species encompass medicinal applications for the treatment of respiratory, antimicrobial, and gynecological diseases. Chemical studies reveal a diverse array of secondary metabolites, including terpenes, flavonoids, and prenylated compounds. [...] Read more.
Piper aduncum L. is widely distributed in tropical regions and the ethnobotanical uses of this species encompass medicinal applications for the treatment of respiratory, antimicrobial, and gynecological diseases. Chemical studies reveal a diverse array of secondary metabolites, including terpenes, flavonoids, and prenylated compounds. Extracts from P. aduncum have shown antibacterial, antifungal, and larvicidal activities. Our study explores the activity of extracts and partitions against Mycobacterium tuberculosis H37Rv, as well as the chemical diversity of the bioactive partition. This marks the first investigation of the bioactive partition of P. aduncum from agroecological cultivation. The ethyl acetate partition from the ethanolic leaf extract (PAEPL) was found to be the most active. PAEPL was subjected to column chromatography using Sephadex LH-20 and the obtained fractions were analyzed using UHPLC-HRMS/MS. The MS/MS data from the fractions were submitted to the online GNPS platform for the generation of the molecular network, which displayed 1714 nodes and 167 clusters. Compounds were identified via manual inspection and different libraries, allowing the annotation of 83 compounds, including flavonoids, benzoic acid derivatives, glycosides, free fatty acids, and glycerol-esterified fatty acids. This study provides the first chemical fingerprint of an antimycobacterial sample from P. aduncum cultivated in an agroecological system. Full article
(This article belongs to the Special Issue Biomanufacturing of Natural Bioactive Compounds)
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Review

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22 pages, 359 KiB  
Review
Progress in the Study of Natural Antimicrobial Active Substances in Pseudomonas aeruginosa
by Tianbo Si, Anqi Wang, Haowen Yan, Lingcong Kong, Lili Guan, Chengguang He, Yiyi Ma, Haipeng Zhang and Hongxia Ma
Molecules 2024, 29(18), 4400; https://doi.org/10.3390/molecules29184400 - 16 Sep 2024
Viewed by 1669
Abstract
The prevalence of antimicrobial resistance reduces the effectiveness of antimicrobial drugs in the prevention and treatment of infectious diseases caused by pathogens such as bacteria, fungi, and viruses. Microbial secondary metabolites have been recognized as important sources for new drug discovery and development, [...] Read more.
The prevalence of antimicrobial resistance reduces the effectiveness of antimicrobial drugs in the prevention and treatment of infectious diseases caused by pathogens such as bacteria, fungi, and viruses. Microbial secondary metabolites have been recognized as important sources for new drug discovery and development, yielding a wide range of structurally novel and functionally diverse antimicrobial drugs for the treatment of a variety of diseases that are considered good producers of novel antimicrobial drugs. Bacteria produce a wide variety of antimicrobial compounds, and thus, antibiotics derived from natural products still dominate over purely synthetic antibiotics among the antimicrobial drugs developed and introduced over the last four decades. Among them, Pseudomonas aeruginosa secondary metabolites constitute a richly diverse source of antimicrobial substances with good antimicrobial activity. Therefore, they are regarded as an outstanding resource for finding novel bioactive compounds. The exploration of antimicrobial compounds among Pseudomonas aeruginosa metabolites plays an important role in drug development and biomedical research. Reports on the secondary metabolites of Pseudomonas aeruginosa, many of which are of pharmacological importance, hold great promise for the development of effective antimicrobial drugs against microbial infections by drug-resistant pathogens. In this review, we attempt to summarize published articles from the last twenty-five years (2000–2024) on antimicrobial secondary metabolites from Pseudomonas aeruginosa. Full article
(This article belongs to the Special Issue Biomanufacturing of Natural Bioactive Compounds)
15 pages, 2183 KiB  
Review
Natural Bioactive Compounds in the Management of Periodontal Diseases: A Comprehensive Review
by Nada Tawfig Hashim, Rasha Babiker, Muhammed Mustahsen Rahman, Riham Mohamed, Sivan Padma Priya, Nallan CSK Chaitanya, Md Sofiqul Islam and Bakri Gobara
Molecules 2024, 29(13), 3044; https://doi.org/10.3390/molecules29133044 - 26 Jun 2024
Cited by 1 | Viewed by 2169
Abstract
Periodontal diseases, chronic inflammatory conditions affecting oral health, are primarily driven by microbial plaque biofilm and the body’s inflammatory response, leading to tissue damage and potential tooth loss. These diseases have significant physical, psychological, social, and economic impacts, necessitating effective management strategies that [...] Read more.
Periodontal diseases, chronic inflammatory conditions affecting oral health, are primarily driven by microbial plaque biofilm and the body’s inflammatory response, leading to tissue damage and potential tooth loss. These diseases have significant physical, psychological, social, and economic impacts, necessitating effective management strategies that include early diagnosis, comprehensive treatment, and innovative therapeutic approaches. Recent advancements in biomanufacturing have facilitated the development of natural bioactive compounds, such as polyphenols, terpenoids, alkaloids, saponins, and peptides, which exhibit antimicrobial, anti-inflammatory, and tissue regenerative properties. This review explores the biomanufacturing processes—microbial fermentation, plant cell cultures, and enzymatic synthesis—and their roles in producing these bioactive compounds for managing periodontal diseases. The integration of these natural compounds into periodontal therapy offers promising alternatives to traditional treatments, potentially overcoming issues like antibiotic resistance and the disruption of the natural microbiota, thereby improving patient outcomes. Full article
(This article belongs to the Special Issue Biomanufacturing of Natural Bioactive Compounds)
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44 pages, 3084 KiB  
Review
Recent Advances in Metabolic Engineering for the Biosynthesis of Phosphoenol Pyruvate–Oxaloacetate–Pyruvate-Derived Amino Acids
by Lianghong Yin, Yanan Zhou, Nana Ding and Yu Fang
Molecules 2024, 29(12), 2893; https://doi.org/10.3390/molecules29122893 - 18 Jun 2024
Cited by 1 | Viewed by 1266
Abstract
The phosphoenol pyruvate–oxaloacetate–pyruvate-derived amino acids (POP-AAs) comprise native intermediates in cellular metabolism, within which the phosphoenol pyruvate–oxaloacetate–pyruvate (POP) node is the switch point among the major metabolic pathways existing in most living organisms. POP-AAs have widespread applications in the nutrition, food, and pharmaceutical [...] Read more.
The phosphoenol pyruvate–oxaloacetate–pyruvate-derived amino acids (POP-AAs) comprise native intermediates in cellular metabolism, within which the phosphoenol pyruvate–oxaloacetate–pyruvate (POP) node is the switch point among the major metabolic pathways existing in most living organisms. POP-AAs have widespread applications in the nutrition, food, and pharmaceutical industries. These amino acids have been predominantly produced in Escherichia coli and Corynebacterium glutamicum through microbial fermentation. With the rapid increase in market requirements, along with the global food shortage situation, the industrial production capacity of these two bacteria has encountered two bottlenecks: low product conversion efficiency and high cost of raw materials. Aiming to push forward the update and upgrade of engineered strains with higher yield and productivity, this paper presents a comprehensive summarization of the fundamental strategy of metabolic engineering techniques around phosphoenol pyruvate–oxaloacetate–pyruvate node for POP-AA production, including L-tryptophan, L-tyrosine, L-phenylalanine, L-valine, L-lysine, L-threonine, and L-isoleucine. Novel heterologous routes and regulation methods regarding the carbon flux redistribution in the POP node and the formation of amino acids should be taken into consideration to improve POP-AA production to approach maximum theoretical values. Furthermore, an outlook for future strategies of low-cost feedstock and energy utilization for developing amino acid overproducers is proposed. Full article
(This article belongs to the Special Issue Biomanufacturing of Natural Bioactive Compounds)
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35 pages, 19299 KiB  
Review
Strategies, Achievements, and Potential Challenges of Plant and Microbial Chassis in the Biosynthesis of Plant Secondary Metabolites
by Taotao Han and Guopeng Miao
Molecules 2024, 29(9), 2106; https://doi.org/10.3390/molecules29092106 - 2 May 2024
Viewed by 2471
Abstract
Diverse secondary metabolites in plants, with their rich biological activities, have long been important sources for human medicine, food additives, pesticides, etc. However, the large-scale cultivation of host plants consumes land resources and is susceptible to pest and disease problems. Additionally, the multi-step [...] Read more.
Diverse secondary metabolites in plants, with their rich biological activities, have long been important sources for human medicine, food additives, pesticides, etc. However, the large-scale cultivation of host plants consumes land resources and is susceptible to pest and disease problems. Additionally, the multi-step and demanding nature of chemical synthesis adds to production costs, limiting their widespread application. In vitro cultivation and the metabolic engineering of plants have significantly enhanced the synthesis of secondary metabolites with successful industrial production cases. As synthetic biology advances, more research is focusing on heterologous synthesis using microorganisms. This review provides a comprehensive comparison between these two chassis, evaluating their performance in the synthesis of various types of secondary metabolites from the perspectives of yield and strategies. It also discusses the challenges they face and offers insights into future efforts and directions. Full article
(This article belongs to the Special Issue Biomanufacturing of Natural Bioactive Compounds)
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