Fatty acid biosynthesis in actinomycetes

All organisms that produce fatty acids do so via a repeated cycle of reactions. In mammals and other animals, these reactions are catalyzed by a type I fatty acid synthase (FAS), a large multifunctional protein to which the growing chain is covalently attached. In contrast, most bacteria (and plants) contain a type II system in which each reaction is catalyzed by a discrete protein. The pathway of fatty acid biosynthesis in Escherichia coli is well established and has provided a foundation for elucidating the type II FAS pathways in other bacteria (White et al., 2005). However, fatty acid biosynthesis is more diverse in the phylum Actinobacteria: Mycobacterium, possess both FAS systems while Streptomyces species have only the multienzyme FAS II system and Corynebacterium species exclusively FAS I. In this review, we present an overview of the genome organization, biochemical properties and physiological relevance of the two FAS systems in the three genera of actinomycetes mentioned above. We also address in detail the biochemical and structural properties of the acyl-CoA carboxylases (ACCases) that catalyzes the first committed step of fatty acid synthesis in actinomycetes, and discuss the molecular bases of their substrate specificity and the structure-based identification of new ACCase inhibitors with antimycobacterial properties.     

Fatty acid structural requirements for leukotriene biosynthesis

Utilizing a variety of fatty acids, differing in chain length, degree and position of unsaturation, we investigated the substrate specificity for the enzymatic production of biologically active slow reacting substances (SRS) and of the other leukotrienes. A cellfree enzyme system obtained from RBL-1 cells was used in this study. The primary structural requirement observed for the conversion by this lipoxygenase enzyme system was a Δ^5,8,11 unsaturation in a polyenoic fatty acid. Such fatty acids as 20:4 (5,8,11,14), 20:5 (5,8,11,14,17), 20:3 (5,8,11), 19:4 (5,8,11,14) and 18:4 (5,8,11,14) were readily converted to compounds that comigrated with 5-HETE and 5,12-DiHETE and to biologically active SRS. Chain length did not have an influence on the formation of these hydroxyacids. Fatty acids with the initial unsaturation at Δ⁴, Δ⁶, Δ⁷ or Δ⁸ were a poor substrate for the leukotriene enzyme system. Therefore, this lipoxygenase pathway in leukocytes is quite different from the lipoxygenase in platelets which does not exhibit this specificity.     

Fatty acid structural requirements for leukotriene biosynthesis

Utilizing a variety of fatty acids, differing in chain length, degree and position of unsaturation, we investigated the substrate specificity for the enzymatic production of biologically active slow reacting substances (SRS) and of the other leukotrienes. A cell-free enzyme system obtained from RBL-1 cells was used in this study. The primary structural requirement observed for the conversion by this lipoxygenase enzyme system was a delta 5,8,11 unsaturation in a polyenoic fatty acid. Such fatty acids as 20:4 (5,8,11,14) 20:5 (5,8,11,14,17), 20:3 (5,8,11), 19:4 (5,8,11,14) and 18:4 (5,8,11,14) were readily converted to compounds that comigrated with 5-HETE and 5,12-DiHETE and to biologically active SRS. Chain length did not have an influence on the formatin of these hydroxyacids. Fatty acids with the initial unsaturation at delta 4, delta 6, delta 7, or delta 8 were a poor substrate for the leukotriene enzyme system. Therefore, this lipoxygenase pathway in leukocytes is quite different from the lipoxygenase in platelets which does not exhibit this specificity.     

Itaconic acid production in microorganisms

Itaconic acid, 2-methylidenebutanedioic acid, is a precursor of polymers, chemicals, and fuels. Many fungi can synthesize itaconic acid; Aspergillus terreus and Ustilago maydis produce up to 85 and 53 g l^?1, respectively. Other organisms, including Aspergillus niger and yeasts, have been engineered to produce itaconic acid. However, the titer of itaconic acid is low compared with the analogous major fermentation product, citric acid, for which the yield is > 200 g l^?1. Here, we review two types of pathway for itaconic acid biosynthesis as well as recent advances by metabolic engineering strategies and process optimization to enhance itaconic acid productivity in native producers and heterologous hosts. We also propose further improvements to overcome existing problems.     

The use of microorganisms in L-ascorbic acid production

L-Ascorbic acid has been industrially produced for around 70 years. Over the past two decades, several innovative bioconversion systems have been proposed in order to simplify the long time market-dominating Reichstein method, a largely chemical synthesis by which still a considerable part of L-ascorbic acid is produced. Here, we describe the current state of biotechnological alternatives using bacteria, yeasts, and microalgae. We also discuss the potential for direct production of l-ascorbic acid exploiting novel bacterial pathways. The advantages of these novel approaches competing with current chemical and biotechnological processes are outlined.     

Fatty acid biosynthesis and dietary regulation in pulmonary adenomas.

Studies of fatty acid metabolism in mouse pulmonary adenomas demonstrate that the alveolar type II cell tumors synthesize fatty acids at a greater rate than either normal or host lungs. This is reflected in elevated levels of both acetyl-CoA (coenzyme A) carboxylase and fatty acid synthase. Carboxylase activity is 4.4-fold, and synthase activity is 7.9-fold higher in the adenomas than normal tissue. Both enzymes from adenomas respond to dietary manipulation in a manner that is qualitatively similar to normal tissue, indicating that the adenomas maintain metabolic control over fatty acid biosynthesis and, therefore, constitute a useful model for normal type II cells. These data suggest that alveolar type II cells have a greater capacity for fatty acid biosynthesis than other cell types of normal lung.     

Fatty acid biosynthesis in liver and adipose tissue from dogs

Production of CO2, fatty acids and glycerol from glucose and acetate was measured in slices of liver and adipose tissue taken from mature dogs. Acetate was the predominant carbon source for de novo fatty acid synthesis in both tissues. Fatty acid synthesis occurred at greater rates in adipose tissue than in liver. Glucose provided carbon for glycerol synthesis production in adipose tissue. Results support the concept that adipose tissue, and not liver, is the principal anatomical site for fatty acid synthesis in dogs.     

Fatty acid biosynthesis in the integument tissue of Triatoma infestans

1. The biosynthesis of lipids and their distribution in several tissues were investigated by injection of 1-14C acetate in females and 5th instar nymphs of the hematophagous hemiptera T. infestans. 2. Biosynthesis of palmitic, palmitoleic, stearic, oleic and very long chain fatty acids up to 26 carbons and hydrocarbons, was shown. They were found in haemolymph, fat body, integument, epicuticle and oocytes with special distribution. 3. Epicuticular hydrocarbon labelling was shown to precede that of haemolymph hydrocarbons. 4. Radioactivity incorporation into each lipid class depends on the developmental stage and the time after injection. 5. "In vitro" incubation of integument tissue with 1-14C acetate demonstrated the biosynthesis of palmitic and stearic acids, a low desaturation to oleic and palmitoleic and an elongation to acids of up to 34 carbons. Hydrocarbons were also synthesized. 6. Haemolymph in the incubation medium has a positive effect on the release of newly-synthesized fatty acid and unsaponifiable material from the integument.     

Towards systems metabolic engineering of microorganisms for amino acid production

Microorganisms capable of efficient production of amino acids have traditionally been developed by random mutation and selection method, which might cause unwanted physiological changes in cellular metabolism. Rational genome-wide metabolic engineering based on systems and synthetic biology tools, which is termed 'systems metabolic engineering', is rising as an alternative to overcome these problems. Recently, several amino acid producers have been successfully developed by systems metabolic engineering, where the metabolic engineering procedures were performed within a systems biology framework, and entire metabolic networks, including complex regulatory circuits, were engineered in an integrated manner. Here we review the current status of systems metabolic engineering successfully applied for developing amino acid producing strains and discuss future prospects.     

工业乳酸发酵的近期进展

乳酸是一种重要的多用途有机酸。通过菌种改良和发酵工艺技术的改进,可以大大提升微生物发酵技术水平,降低成本。简要综述有关的研究进展。     

Fatty acid production by heterotrophic Chlorella saccharophila

The fatty acid composition of the alga Chlorella saccharophila was investigated under different growth conditions. Using glucose as the sole carbon source, heterotrophically-grown Chlorella saccharophila produced a greater proportion of the polyunsaturated fatty acids (C18: 2 and C18: 3) than photosynthetic cultures, with linoleic acid (C18: 2) predominating. An unexpected discovery was the observation that at the lowest glucose concentration (2.5 gl^–1) the lipid content of the algae increased to between 36–47% of the cell weight, depending on the temperature. At glucose concentrations of 5 g l^–1 or more, the lipid content fell to 10–12% of the cell, although total fatty acid yield was higher due to higher biomass concentrations. Aeration of heterotrophic cultures promoted the production of unsaturated fatty acids compared to non-aerated cultures.