scholarly journals Microbial Biosynthesis of Lactones: Gaps and Opportunities towards Sustainable Production

2021 ◽  
Vol 11 (18) ◽  
pp. 8500
Author(s):  
Rui Silva ◽  
Eduardo Coelho ◽  
Tatiana Q. Aguiar ◽  
Lucília Domingues

Lactones are volatile organic compounds widely present in foods. These chemicals are applied as flavors and fragrances in the food, cosmetics and pharmaceutical industries. Recently, the potential of lactones as green solvents and fuel precursors reinforced their role as platform compounds of future bio-based economies. However, their current mode of production needs to change. Lactones are mainly obtained through chemical synthesis or microbial biotransformation of hydroxy fatty acids. The latter approach is preferred but still needs to use more sustainable substrates. Hydroxy fatty acids are non-abundant and non-sustainable substrates from environmental, health and economic points of view. Therefore, it is urgent to identify and engineer microorganisms with the rare ability to biosynthesize lactones from carbohydrates or renewable lipids. Here, we firstly address the variety and importance of lactones. Then, the current understanding of the biosynthetic pathways involved in lactone biosynthesis is presented, making use of the knowledge acquired in microorganisms and fruits. From there, we present and make the distinction between biotransformation processes and de novo biosynthesis of lactones. Finally, the opportunities and challenges towards more sustainable production in addition to the relevance of two well-known industrial microbes, the filamentous fungus Ashbya gossypii and the yeast Yarrowia lipolytica, are discussed.

2020 ◽  
Vol 27 ◽  
Author(s):  
Justyna Dłubek ◽  
Jacek Rysz ◽  
Zbigniew Jabłonowski ◽  
Anna Gluba-Brzózka ◽  
Beata Franczyk

: Prostate cancer is second most common cancer affecting male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signalling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signalling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with higher risk of more aggressive course of disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, it constitutes an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aimed to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (stearoyl-CoA desaturase) in particular, may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of the circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions, or even sub-fractions of e.g. HDL cholesterol.


1995 ◽  
Vol 269 (2) ◽  
pp. E247-E252 ◽  
Author(s):  
H. O. Ajie ◽  
M. J. Connor ◽  
W. N. Lee ◽  
S. Bassilian ◽  
E. A. Bergner ◽  
...  

To determine the contributions of preexisting fatty acid, de novo synthesis, and chain elongation in long-chain fatty acid (LCFA) synthesis, the synthesis of LCFAs, palmitate (16:0), stearate (18:0), arachidate (20:0), behenate (22:0), and lignocerate (24:0), in the epidermis, liver, and spinal cord was determined using deuterated water and mass isotopomer distribution analysis in hairless mice and Sprague-Dawley rats. Animals were given 4% deuterated water for 5 days or 8 wk in their drinking water. Blood was withdrawn at the end of these times for the determination of deuterium enrichment, and the animals were killed to isolate the various tissues for lipid extraction for the determination of the mass isotopomer distributions. The mass isotopomer distributions in LCFA were incompatible with synthesis from a single pool of primer. The synthesis of palmitate, stearate, arachidate, behenate, and lignocerate followed the expected biochemical pathways for the synthesis of LCFAs. On average, three deuterium atoms were incorporated for every addition of an acetyl unit. The isotopomer distribution resulting from chain elongation and de novo synthesis can be described by the linear combination of two binomial distributions. The proportions of preexisting, chain elongation, and de novo-synthesized fatty acids as a percentage of the total fatty acids were determined using multiple linear regression analysis. Fractional synthesis was found to vary, depending on the tissue type and the fatty acid, from 47 to 87%. A substantial fraction (24-40%) of the newly synthesized molecules was derived from chain elongation of unlabeled (recycled) palmitate.


2021 ◽  
Vol 9 (6) ◽  
pp. 1290
Author(s):  
Natalia Alvarez-Santullano ◽  
Pamela Villegas ◽  
Mario Sepúlveda Mardones ◽  
Roberto E. Durán ◽  
Raúl Donoso ◽  
...  

Burkholderia sensu lato (s.l.) species have a versatile metabolism. The aims of this review are the genomic reconstruction of the metabolic pathways involved in the synthesis of polyhydroxyalkanoates (PHAs) by Burkholderia s.l. genera, and the characterization of the PHA synthases and the pha genes organization. The reports of the PHA synthesis from different substrates by Burkholderia s.l. strains were reviewed. Genome-guided metabolic reconstruction involving the conversion of sugars and fatty acids into PHAs by 37 Burkholderia s.l. species was performed. Sugars are metabolized via the Entner–Doudoroff (ED), pentose-phosphate (PP), and lower Embden–Meyerhoff–Parnas (EMP) pathways, which produce reducing power through NAD(P)H synthesis and PHA precursors. Fatty acid substrates are metabolized via β-oxidation and de novo synthesis of fatty acids into PHAs. The analysis of 194 Burkholderia s.l. genomes revealed that all strains have the phaC, phaA, and phaB genes for PHA synthesis, wherein the phaC gene is generally present in ≥2 copies. PHA synthases were classified into four phylogenetic groups belonging to class I II and III PHA synthases and one outlier group. The reconstruction of PHAs synthesis revealed a high level of gene redundancy probably reflecting complex regulatory layers that provide fine tuning according to diverse substrates and physiological conditions.


1963 ◽  
Vol 4 (2) ◽  
pp. 139-143 ◽  
Author(s):  
Yasuo Kishimoto ◽  
Norman S. Radin

Catalysts ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 665
Author(s):  
Li Zong ◽  
Yan Zhang ◽  
Zhengkang Shao ◽  
Yingwu Wang ◽  
Zheng Guo ◽  
...  

Cytochrome P450 (CYP) mediated enzymatic hydroxylation of fatty acids present a green alternative to chemical synthesis of hydroxy fatty acids (HFAs), which are high-value oleochemicals with various uses in materials industry and medical field. Although many CYPs require the presence of additional reductase proteins for catalytic activity, self-sufficient CYPs have their reductase partner naturally fused into their catalytic domain, leading to a greatly simplified biotransformation process. A recently discovered self-sufficient CYP, BAMF2522 from Bacillus amyloliquefaciens DSM 7, exhibits novel regioselectivity by hydroxylating in-chain positions of palmitic acid generating ω-1 to ω-7 HFAs, a rare regiodiversity profile among CYPs. Besides, F89I mutant of BAMF2522 expanded hydroxylation up to ω-9 position of palmitic acid. Here, we further characterize this enzyme by determining optimum temperature and pH as well as thermal stability. Moreover, using extensive site-directed and site-saturation mutagenesis, we obtained BAMF2522 variants that demonstrate greatly increased regioselectivity for in-chain positions (ω-4 to ω-9) of various medium to long chain fatty acids. Remarkably, when a six-residue mutant was reacted with palmitic acid, 84% of total product content was the sum of ω-7, ω-8 and ω-9 HFA products, the highest in-chain selectivity observed to date with a self-sufficient CYP. In short, our study demonstrates the potential of a recently identified CYP and its mutants for green and sustainable production of a variety of in-chain hydroxy enriched HFAs.


Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 128
Author(s):  
Leonel Pereira ◽  
Ana Valado

Edible marine algae are rich in bioactive compounds and are, therefore, a source of bioavailable proteins, long chain polysaccharides that behave as low-calorie soluble fibers, metabolically necessary minerals, vitamins, polyunsaturated fatty acids, and antioxidants. Marine algae were used primarily as gelling agents and thickeners (phycocolloids) in food and pharmaceutical industries in the last century, but recent research has revealed their potential as a source of useful compounds for the pharmaceutical, medical, and cosmetic industries. The green, red, and brown algae have been shown to have useful therapeutic properties in the prevention and treatment of neurodegenerative diseases: Parkinson, Alzheimer’s, and Multiple Sclerosis, and other chronic diseases. In this review are listed and described the main components of a suitable diet for patients with these diseases. In addition, compounds derived from macroalgae and their neurophysiological activities are described.


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