scholarly journals Engineering Aspergillus oryzae for the Heterologous Expression of a Bacterial Modular Polyketide Synthase

2021 ◽  
Vol 7 (12) ◽  
pp. 1085
Author(s):  
Jin Feng ◽  
Maurice Hauser ◽  
Russell J. Cox ◽  
Elizabeth Skellam
Keyword(s):  
Natural Products ◽  
Aspergillus Oryzae ◽  
Polyketide Synthase ◽  
Biological Activities ◽  
Alternative Host ◽  
Coding Region ◽  
Drug Discovery And Development ◽  
Modular Polyketide Synthase ◽  
Microbial Natural Products ◽  
Synthesis And Degradation

Microbial natural products have had phenomenal success in drug discovery and development yet form distinct classes based on the origin of their native producer. Methods that enable metabolic engineers to combine the most useful features of the different classes of natural products may lead to molecules with enhanced biological activities. In this study, we modified the metabolism of the fungus Aspergillus oryzae to enable the synthesis of triketide lactone (TKL), the product of the modular polyketide synthase DEBS1-TE engineered from bacteria. We established (2S)-methylmalonyl-CoA biosynthesis via introducing a propionyl-CoA carboxylase complex (PCC); reassembled the 11.2 kb DEBS1-TE coding region from synthetic codon-optimized gene fragments using yeast recombination; introduced bacterial phosphopantetheinyltransferase SePptII; investigated propionyl-CoA synthesis and degradation pathways; and developed improved delivery of exogenous propionate. Depending on the conditions used titers of TKL ranged from <0.01–7.4 mg/L. In conclusion, we have demonstrated that A. oryzae can be used as an alternative host for the synthesis of polyketides from bacteria, even those that require toxic or non-native substrates. Our metabolically engineered A. oryzae may offer advantages over current heterologous platforms for producing valuable and complex natural products.

scholarly journals Recent Advances in Discovery of Lead Structures from Microbial Natural Products: Genomics- and Metabolomics-Guided Acceleration

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2542
Author(s):  
Linda Sukmarini
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Screening Methods ◽  
Technological Advancement ◽  
Natural Origin ◽  
Drug Discovery And Development ◽  
New Methodologies ◽  
Analytical Instrumentation ◽  
Microbial Natural Products ◽  
Drug Leads

Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. They offer major opportunities for finding novel lead structures that are active against a broad spectrum of assay targets, particularly those from secondary metabolites of microbial origin. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques. Aided by the more in-depth understanding of different biosynthetic pathways and the technological advancement in analytical instrumentation, the development of new methodologies provides an alternative that can accelerate discoveries of new lead-structures of natural origin. This present mini-review briefly discusses selected examples regarding advancements in bioinformatics and genomics (focusing on genome mining and metagenomics approaches), as well as bioanalytics (mass-spectrometry) towards the microbial NPs-based drug discovery and development. The selected recent discoveries from 2015 to 2020 are featured herein.

Computational Studies on the Substrate Specificity of an Acyltransferase Domain from Salinomycin Polyketide Synthase

2021 ◽  
Author(s):  
Huining Ji ◽  
Ting Shi ◽  
Lei Liu ◽  
Fa Zhang ◽  
Wentao Tao ◽  
...  
Keyword(s):  
Natural Products ◽  
Substrate Specificity ◽  
Polyketide Synthase ◽  
Coenzyme A ◽  
Biological Activities ◽  
Polyketide Synthases ◽  
Short Chain ◽  
Computational Studies ◽  
Chemical Structures ◽  
Coa Thioesters

Polyketides are a large group of natural products with diverse chemical structures and biological activities. They are biosynthesized by modular polyketide synthases (PKSs) from coenzyme A (CoA) thioesters of short-chain...

scholarly journals Chiral Derivatives of Xanthones with Antimicrobial Activity

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 314 ◽  
Author(s):  
Joana Araújo ◽  
Carla Fernandes ◽  
Madalena Pinto ◽  
Maria Tiritan
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Drug Discovery ◽  
Biological Activities ◽  
World Health ◽  
Natural Sources ◽  
Drug Discovery And Development ◽  
The World ◽  
Health Organization ◽  
Derivatives Of

According to the World Health Organization, the exacerbated use of antibiotics worldwide is increasing multi-resistant infections, especially in the last decade. Xanthones are a class of compounds receiving great interest in drug discovery and development that can be found as natural products or obtained by synthesis. Many derivatives of xanthones are chiral and associated with relevant biological activities, including antimicrobial. The aim of this review is to compile information about chiral derivatives of xanthones from natural sources and their synthesized examples with antimicrobial activity.

scholarly journals Culturable Microorganisms Associated with Sea Cucumbers and Microbial Natural Products

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 461
Author(s):  
Lei Chen ◽  
Xiao-Yu Wang ◽  
Run-Ze Liu ◽  
Guang-Yu Wang
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Sea Cucumber ◽  
Marine Invertebrates ◽  
Biological Activities ◽  
Sea Cucumbers ◽  
Bioactive Natural Products ◽  
Microbial Natural Products ◽  
Current List

Sea cucumbers are a class of marine invertebrates and a source of food and drug. Numerous microorganisms are associated with sea cucumbers. Seventy-eight genera of bacteria belonging to 47 families in four phyla, and 29 genera of fungi belonging to 24 families in the phylum Ascomycota have been cultured from sea cucumbers. Sea-cucumber-associated microorganisms produce diverse secondary metabolites with various biological activities, including cytotoxic, antimicrobial, enzyme-inhibiting, and antiangiogenic activities. In this review, we present the current list of the 145 natural products from microorganisms associated with sea cucumbers, which include primarily polyketides, as well as alkaloids and terpenoids. These results indicate the potential of the microorganisms associated with sea cucumbers as sources of bioactive natural products.

Secondary Metabolites from Deep-Sea Derived Microorganisms

2020 ◽  
Vol 27 (36) ◽  
pp. 6244-6273 ◽  
Author(s):  
Chunxiao Sun ◽  
Shah Mudassir ◽  
Zhenzhen Zhang ◽  
Yanyan Feng ◽  
Yimin Chang ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Small Molecules ◽  
Deep Sea ◽  
Biological Activities ◽  
Structural Characteristics ◽  
Chemical Structures ◽  
Pharmaceutical Agents ◽  
Microbial Natural Products ◽  
Cytotoxic Function

Microorganisms obtained from the deep sea are a rich source of marine natural products with distinctive chemical structures and bioactivities. In this review, we will provide a retrospective of outstanding research within the scope of deep-sea (≥1000 m) microbial natural products, which has produced up to 442 compounds by the end of 2017. Approximetely, 60% of these structures have demonstrated various biological activities with more than 30% showing cytotoxic function. In this review, we particularly summarize those successful research on secondary metabolites produced by deep-sea derived microorganisms with inclusion of structural characteristics, biological activities, together with biogenetic origins and taxonomic features of the source microorganisms, from which, we expect to provide more comprehensive understanding of small molecules obtained from deep-sea environment and benefit the ongoing scholarly endeavors in the search for novel pharmaceutical agents from the deep-sea derived microorganisms.

scholarly journals Chemical Diversity and Biological Activities of Phaeosphaeria Fungi Genus: A Systematic Review

2018 ◽  
Vol 4 (4) ◽  
pp. 130 ◽  
Author(s):  
Am El-Demerdash
Keyword(s):  
Systematic Review ◽  
Natural Products ◽  
Cyclic Peptides ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Wide Scope ◽  
Lead Discovery ◽  
Chemical Structures ◽  
Drug Lead ◽  
Microbial Natural Products

Microbial natural products (MNPs) have been identified as important hotspots and effective sources for drug lead discovery. The genus Phaeosphaeria (family: Phaeosphaeriaceae, order: Pleosporales), in particular, has produced divergent chemical structures, including pyrazine alkaloids, isocoumarins, perylenequinones, anthraquinones, diterpenes, and cyclic peptides, which display a wide scope of biological potentialities. This contribution comprehensively highlights, over the period 1974–2018, the chemistry and biology of the isolated natural products from the micro-filamentous Phaeosphaeria fungi genus. A list of 71 compounds, with structural and biological diversities, were gathered into 5 main groups.

Pyrone-derived Marine Natural Products: A Review on Isolation, Bio-activities and Synthesis

2020 ◽  
Vol 24 (4) ◽  
pp. 354-401 ◽  
Author(s):  
Keisham S. Singh
Keyword(s):  
Natural Products ◽  
Marine Natural Products ◽  
Marine Fungi ◽  
Kojic Acid ◽  
Biological Activities ◽  
Biological Significance ◽  
Pyrone Ring ◽  
Enol Ethers ◽  
Bioactive Natural Products ◽  
Marine Metabolites

Marine natural products (MNPs) containing pyrone rings have been isolated from numerous marine organisms, and also produced by marine fungi and bacteria, particularly, actinomycetes. They constitute a versatile structure unit of bioactive natural products that exhibit various biological activities such as antibiotic, antifungal, cytotoxic, neurotoxic, phytotoxic and anti-tyrosinase. The two structure isomers of pyrone ring are &#947;- pyrone and &#945;-pyrone. In terms of chemical motif, &#947;-pyrone is the vinologous form of &#945;- pyrone which possesses a lactone ring. Actinomycete bacteria are responsible for the production of several &#945;-pyrone compounds such as elijopyrones A-D, salinipyrones and violapyrones etc. to name a few. A class of pyrone metabolites, polypropionates which have fascinating carbon skeleton, is primarily produced by marine molluscs. Interestingly, some of the pyrone polytketides which are found in cone snails are actually synthesized by actinomycete bacteria. Several pyrone derivatives have been obtained from marine fungi such as Aspergillums flavus, Altenaria sp., etc. The &#947;-pyrone derivative namely, kojic acid obtained from Aspergillus fungus has high commercial demand and finds various applications. Kojic acid and its derivative displayed inhibition of tyrosinase activity and, it is also extensively used as a ligand in coordination chemistry. Owing to their commercial and biological significance, the synthesis of pyrone containing compounds has been given attention over the past years. Few reviews on the total synthesis of pyrone containing natural products namely, polypropionate metabolites have been reported. However, these reviews skipped other marine pyrone metabolites and also omitted discussion on isolation and detailed biological activities. This review presents a brief account of the isolation of marine metabolites containing a pyrone ring and their reported bio-activities. Further, the review covers the synthesis of marine pyrone metabolites such as cyercene-A, placidenes, onchitriol-I, onchitriol-II, crispatene, photodeoxytrichidione, (-) membrenone-C, lihualide-B, macrocyclic enol ethers and auripyrones-A & B.

scholarly journals Natural products isolated from Casimiroa

2020 ◽  
Vol 18 (1) ◽  
pp. 778-797
Author(s):  
Khun Nay Win Tun ◽  
Nanik Siti Aminah ◽  
Alfinda Novi Kristanti ◽  
Hnin Thanda Aung ◽  
Yoshiaki Takaya
Keyword(s):  
Natural Products ◽  
Spectral Data ◽  
Aromatic Compounds ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Quinoline Alkaloids

AbstractAbout 140 genera and more than 1,600 species belong to the Rutaceae family. They grow in temperate and tropical zones on both hemispheres, as trees, shrubs, and herbs. Casimiroa is one of the genera constituting 13 species, most of which are found in tropical and subtropical regions. Many chemical constituents have been derived from this genus, including quinoline alkaloids, flavonoids, coumarins, and N-benzoyltyramide derivatives. This article reviews different studies carried out on aromatic compounds of genus Casimiroa; their biological activities; the different skeletons of coumarins, alkaloids, flavonoids, and others; and their characteristic NMR spectral data.

Enzymatic dimerization in the biosynthetic pathway of microbial natural products

2021 ◽  
Author(s):  
Jiawang Liu ◽  
Anan Liu ◽  
Youcai Hu
Keyword(s):  
Natural Products ◽  
Biosynthetic Pathway ◽  
Structural Diversity ◽  
Cytochrome P450s ◽  
Microbial Natural Products

Cytochrome P450s, laccases, and intermolecular [4 + 2] cyclases, along with other enzymes were utilized to catalyze varied dimerization of matured natural products so as to create the structural diversity and complexity in microorganisms.

Sign in / Sign up

Export Citation Format

Share Document