Constructing High-Yielding for (-)-α-Bisabolol Production Based on the Exogenous Haloarchaeal MVA Pathway and Endogenous Molecular Chaperones.

(-)-α-Bisabolol exhibits analgesic, anti-inflammatory, and skin-soothing properties and is widely applied in the cosmetic and pharmaceutical industries. The use of plant essential oil distillation or chemical synthesis to produce (-)-α-bisabolol is both inefficient and unsustainable. Currently, the microbial production of (-)-α-bisabolol mainly relies on and as chassis strains; however, high concentrations of (-)-α-bisabolol have certain toxicity to the strain.

Deciphering the roles of bacterial and fungal communities in the formation and quality of agarwood.

Aquilaria sinensis is a significant resin-producing plant worldwide that is crucial for agarwood production. Agarwood has different qualities depending on the method with which it is formed, and the microbial community structures that are present during these methods are also diverse. Furthermore, the microbial communities of plants play crucial roles in determining their health and productivity.

Characterization and Application of an Aspartate Dehydrogenase from Achromobacter denitrificans.

A novel gene encoding aspartate dehydrogenase (ASPDH) has been discovered in Achromobacter denitrificans. The product of this gene has a strict dependence on NADH and demonstrated significant reductive activity towards not only oxaloacetate (OAA) but also 2-ketobutyric acid. Further enzymatic characterization revealed the kinetic parameters of ASPDH for OAA and 2-ketobutyric acid were as follows: K values of 4.

Characterization and Application of a Stationary Phase Promoter Library from .

has garnered increasing attention as a promising host for valuable compound production. However, the lack of an efficient gene regulation toolkit severely hampers its applications. Here, a library of stationary phase promoters was screened in HBA7 using RNA-seq and RT-qPCR, revealing a 43-fold regulatory range with the red fluorescent protein mKate2 as the reporter.

Construction and characterization of a promoter library with varying strengths to enhance acetoin production from xylose in Serratia marcescens.

Serratia marcescens is utilized as a significant enterobacteria in the production of various high-value secondary metabolites. Acetoin serves as a crucial foundational compound of development and finds application in a broad range of fields. Furthermore, S.

Enzymatic properties of ornithine decarboxylase from Clostridium aceticum DSM1496.

Clostridium aceticum DSM1496 is an acid-resistant strain in which ornithine decarboxylase (ODC) plays a crucial role in acid resistance. In this study, we expressed ODC derived from C. aceticum DSM1496 in Escherichia coli BL21 (DE3) and thoroughly examined its enzymatic properties.

prediction and biological assessment of novel angiogenesis modulators from traditional Chinese medicine.

Uncontrolled angiogenesis is a common denominator underlying many deadly and debilitating diseases such as myocardial infarction, chronic wounds, cancer, and age-related macular degeneration. As the current range of FDA-approved angiogenesis-based medicines are far from meeting clinical demands, the vast reserve of natural products from traditional Chinese medicine (TCM) offers an alternative source for developing pro-angiogenic or anti-angiogenic modulators. Here, we investigated 100 traditional Chinese medicine-derived individual metabolites which had reported gene expression in MCF7 cell lines in the Gene Expression Omnibus (GSE85871).

Advances and perspectives on perylenequinone biosynthesis.

Under illumination, the fungal secondary metabolites, perylenequinones (PQs) react with molecular oxygen to generate reactive oxygen species (ROS), which, in excess can damage cellular macromolecules and trigger apoptosis. Based on this property, PQs have been widely used as photosensitizers and applied in pharmaceuticals, which has stimulated research into the discovery of new PQs and the elucidation of their biosynthetic pathways. The PQs-associated literature covering from April 1967 to September 2022 is reviewed in three sections: (1) the sources, structural diversity, and biological activities of microbial PQs; (2) elucidation of PQ biosynthetic pathways, associated genes, and mechanisms of regulation; and (3) advances in pathway engineering and future potential strategies to modify cellular metabolism and improve PQ production.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×10/L or hsCRP ≥ 3.

Highly efficient biosynthesis of spermidine from L-homoserine and putrescine using an engineered Escherichia coli with NADPH self-sufficient system.

Spermidine is an important polyamine that can be used for the synthesis of various bioactive compounds in the food and pharmaceutical fields. In this study, a novel efficient whole-cell biocatalytic method with an NADPH self-sufficient cycle for spermidine biosynthesis was designed and constructed by co-expressing homoserine dehydrogenase (HSD), carboxyspermidine dehydrogenase (CASDH), and carboxyspermidine decarboxylase (CASDC). First, the enzyme-substrate coupled cofactor regeneration system from co-expression of NADP-dependent ScHSD and NADPH-dependent AfCASDH exactly provides an efficient method for cofactor cycling.

Secondary Metabolites of : Metabolism and Medicinal Value.

(scientific name: (Thunb.) Lour.) is a species of the genus in the family Oleaceae, and it has a long history of cultivation in China.

Overexpression and biochemical characterization of a carboxyspermidine dehydrogenase from Agrobacterium fabrum str. C58 and its application to carboxyspermidine production.

Background: Carboxyspermidine (C-Spd) is a potentially valuable polyamine carboxylate compound and an excellent building block for spermidine synthesis, which is a critical polyamine with significant implications for human health and longevity. C-Spd can also be used to prepare multivalent cationic lipids and modify nucleoside probes. Because of these positive effects on human health, C-Spd is of considerable interest as a food additive and pharmaceutical target.

Characterization of a putative tropinone reductase from Tarenaya hassleriana with a broad substrate specificity.

A novel short-chain alcohol dehydrogenase from Tarenaya hassleriana labeled as putative tropinone reductase was heterologously expressed in Escherichia coli. Purified recombinant protein had molecular weight of approximately 30 kDa on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. T.

Prediction and identification of synergistic compound combinations against pancreatic cancer cells.

Resistance to current therapies is common for pancreatic cancer and hence novel treatment options are urgently needed. In this work, we developed and validated a computational method to select synergistic compound combinations based on transcriptomic profiles from both the disease and compound side, combined with a pathway scoring system, which was then validated prospectively by testing 30 compounds (and their combinations) on PANC-1 cells. Some compounds selected as single agents showed lower GI50 values than the standard of care, gemcitabine.

Biosynthesis of phenylpyruvic acid from l-phenylalanine using chromosomally engineered Escherichia coli.

The efficiency of whole-cell biotransformation is often affected by the genetic instability of plasmid-based expression systems, which require selective pressure to maintain the stability of the plasmids. To circumvent this shortcoming, we constructed a chromosome engineering strain for the synthesis of phenylpyruvic acid (PPA) from l-phenylalanine. First, l-amino acid deaminase (pmLAAD) from Proteus myxofaciens was incorporated into Escherichia coli BL21 (DE3) chromosome and the copy numbers of pmLAAD were increased by chemically induced chromosomal evolution (CIChE).

Converting the 3-quinuclidinone reductase from Agrobacterium tumefaciens into the ethyl 4-chloroacetoacetate reductase by site-directed mutagenesis.

In this study, the 3-quinuclidinone reductase from Agrobacterium tumefaciens (AtQR) was modified by site-directed mutagenesis. And we further obtained a saturation mutant library in which the residue 197 was mutated. A single-point mutation converted the wild enzyme that originally had no catalytic activity in reduction of ethyl 4-chloroacetoacetate (COBE) into an enzyme with catalytic activity.

Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways.

Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood.

Modular engineering of Shiraia bambusicola for hypocrellin production through an efficient CRISPR system.

Shiraia bambusicola exhibits an excellent capability to produce high-value pharmacological drugs, such as hypocrellin. However, less effective molecular tools hamper the processes to discover or exploit these metabolites. To address this issue, the more effective CRISPR/Cas9 system was constructed by optimizing the sgRNA transcription elements and disrupting the endogenous non-homologous end-joining pathway.

Unveiling the Multipath Biosynthesis Mechanism of 2-Phenylethanol in .

could convert l-phenylalanine into 2-phenylethanol (2-PE) via the Ehrlich pathway, the amino acid deaminase pathway, and the aromatic amino acid decarboxylase pathway. The aromatic amino acid decarboxylase pathway was proved for the first time in . In this pathway, l-aromatic amino acid transferase demonstrated a unique catalytic property, transforming 2-penylethylamine into phenylacetaldehyde.

A novel type alanine dehydrogenase from Helicobacter aurati: Molecular characterization and application.

A novel alanine dehydrogenase (ADH; EC.1.4.

A novel feruloyl esterase with high rosmarinic acid hydrolysis activity from Bacillus pumilus W3.

A novel feruloyl esterase (BpFae12) with rosmarinic acid (RA) hydrolysis activity was isolated from Bacillus pumilus W3 and expressed in Escherichia coli BL21 (DE3). With RA as a substrate, the optimal pH and temperature of BpFae12 were pH 8.0 and 50 °C, respectively.

Advanced strategy for metabolite exploration in filamentous fungi.

Filamentous fungi comprise an abundance of gene clusters that encode high-value metabolites, whereas affluent gene clusters remain silent during laboratory conditions. Complex cellular metabolism further limits these metabolite yields. Therefore, diverse strategies such as genetic engineering and chemical mutagenesis have been developed to activate these cryptic pathways and improve metabolite productivity.

Production of rosmarinic acid with ATP and CoA double regenerating system.

Rosmarinic acid (RA), as a hydroxycinnamic acid ester of caffeic acid (CA) and 3,4-dihydroxyphenyllactic acid (3,4-DHPL), is a phenylpropanoid-derived plant natural product and has diverse biological activities. This work acts as a modular platform for microbial production using a two-cofactor (ATP and CoA) regeneration system to product RA based on a cell-free biosynthetic approach. Optimal activity of the reaction system was pH 8 and 30 °C.

Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study.

Inspired by the traditional Chinese herbal pair of Polygala tenuifolia-Acori Tatarinowii for treating epilepsy, 33 novel substituted cinnamic α-asaronol esters and analogues were designed by Combination of Traditional Chinese Medicine Molecular Chemistry (CTCMMC) strategy, synthesized and tested systematically not only for anticonvulsant activity in three mouse models but also for LDH inhibitory activity. Thereinto, 68-70 and 75 displayed excellent and broad spectra of anticonvulsant activities with modest ability in preventing neuropathic pain, as well as low neurotoxicity. The protective indices of these four compounds compared favorably with stiripentol, lacosamide, carbamazepine and valproic acid.