The discovery of penicillin by Sir Alexander Fleming in 1928 provided us with access to a new class of compounds useful at fighting bacterial infections: antibiotics. Ever since, a number of studies were carried out to find new molecules with the same activity. Microorganisms belonging to Actinobacteria phylum, the Actinomycetes, were the most important sources of antibiotics. Bioactive compounds isolated from this order were also an important inspiration reservoir for pharmaceutical chemists who realized the synthesis of new molecules with antibiotic activity. According to the World Health Organization (WHO), antibiotic resistance is currently one of the biggest threats to global health, food security, and development. The world urgently needs to adopt measures to reduce this risk by finding new antibiotics and changing the way they are used. In this review, we describe the primary role of Actinomycetes in the history of antibiotics. Antibiotics produced by these microorganisms, their bioactivities, and how their chemical structures have inspired generations of scientists working in the synthesis of new drugs are described thoroughly.

In this work, we studied the biotechnological potential of thirteen probiotic microorganisms currently used to improve human health. We discovered that the majority of the investigated bacteria are able to catalyze the hydration reaction of the unsaturated fatty acids (UFAs). We evaluated their biocatalytic activity toward the three most common vegetable UFAs, namely oleic, linoleic, and linolenic acids. The whole-cell biotransformation experiments were performed using a fatty acid concentration of 3 g/L in anaerobic conditions. Through these means, we assessed that the main part of the investigated strains catalyzed the hydration reaction of UFAs with very high regio- and stereoselectivity. Our biotransformation reactions afforded almost exclusively 10-hydroxy fatty acid derivatives with the single exception of Lactobacillus acidophilus ATCC SD5212, which converted linoleic acid in a mixture of 13-hydroxy and 10-hydroxy derivatives. Oleic, linoleic, and linolenic acids were transformed into (R)-10-hydroxystearic acid, (S)-(12Z)-10-hydroxy-octadecenoic, and (S)-(12Z,15Z)-10-hydroxy-octadecadienoic acids, respectively, usually with very high enantiomeric purity (ee > 95%). It is worth noting that the biocatalytic capabilities of the thirteen investigated strains may change considerably from each other, both in terms of activity, stereoselectivity, and transformation yields. Lactobacillus rhamnosus ATCC 53103 and Lactobacillus plantarum 299 V proved to be the most versatile, being able to efficiently and selectively hydrate all three investigated fatty acids.

Microbial conversion of oleic acid (1) to form value-added industrial products has gained increasing scientific and economic interest. So far, the production of natural lactones with flavor and fragrance properties from fatty acids by non-genetically modified organisms (non-GMO) involves whole cells of bacteria catalyzing the hydration of unsaturated fatty acids as well as yeast strains responsible for further β-oxidation processes. Development of a non-GMO process, involving a sole strain possessing both enzymatic activities, significantly lowers the costs of the process and constitutes a better method from the customers’ point of view regarding biosafety issues. Twenty bacteria from the genus of Bacillus, Comamonas, Dietzia, Gordonia, Micrococcus, Pseudomonas, Rhodococcus and Streptomyces were screened for oxidative functionalization of oleic acid (1). Micrococcus luteus PCM525 was selected as the sole strain catalyzing the one-pot transformation of oleic acid (1) into natural valuable peach and strawberry-flavored γ-dodecalactone (6) used in the food, beverage, cosmetics and pharmaceutical industries. Based on the identified products formed during the process of biotransformation, we clearly established a pathway showing that oleic acid (1) is hydrated to 10-hydroxystearic acid (2), then oxidized to 10-ketostearic acid (3), giving 4-ketolauric acid (4) after three cycles of β-oxidation, which is subsequently reduced and cyclized to γ-dodecalactone (6) (Scheme 1). Moreover, three other strains (Rhodococcus erythropolis DSM44534, Rhodococcus ruber PCM2166, Dietzia sp. DSM44016), with high concomitant activities of oleate hydratase and alcohol dehydrogenase, were identified as efficient producers of 10-ketostearic acid (3), which can be used in lubricant and detergent formulations. Considering the prevalence of γ-dodecalactone (6) and 10-ketostearic acid (3) applications and the economic benefits of sustainable management, microbial bioconversion of oleic acid (1) is an undeniably attractive approach.

Natural hydroxy fatty acids are relevant starting materials for the production of a number of industrial fine chemicals, such as different high-value flavour ingredients. Only a few of the latter hydroxy acid derivatives are available on a large scale. Therefore, their preparation by microbial hydration of unsaturated fatty acids, affordable from vegetable oils, is a new biotechnological challenge. In this study, we describe the use of the probiotic bacterium Lactobacillus rhamnosus (ATCC 53103) as whole-cell biocatalyst for the hydration of the most common unsaturated octadecanoic acids, namely oleic acid, linoleic acid, and linolenic acid. We discovered that the addition of the latter fatty acids to an anaerobic colture of the latter strain, during the early stage of its exponential growth, allows the production of the corresponding mono-hydroxy derivatives. In these experimental conditions, the hydration reaction proceeds with high regio- and stereoselectivity. Only 10-hydroxy derivatives were formed and the resulting (R)-10-hydroxystearic acid, (S)-(12Z)-10-hydroxy-octadecenoic acid, and (S)-(12Z,15Z)-10-hydroxy-octadecadienoic acid were obtained in very high enantiomeric purity (ee > 95%). Although overall conversions usually do not exceed 50% yield, our biotransformation protocol is stereoselective, scalable, and holds preparative significance.

Recently, we described the preparation of the recombinant oleate hydratase from Lactobacillus rhamnosus ATCC 53103. We observed that the purified C-terminal His-tagged enzyme was completely inactive and the catalytic activity was partially restored only in presence of a large amount of flavin adenine dinucleotide (FAD). In the present work, we assess that this hydratase in the presence of the reduced form of flavin adenine dinucleotide (FADH₂) is at least one hundred times as active as in the presence of the same concentration of FAD. By means of two different biochemical processes, we demonstrated unambiguously that oleate hydratase from Lactobacillus rhamnosus ATCC 53103 is a FADH₂-dependent enzyme. As a first relevant application of this discovery, we devised a preparative procedure for the stereoselective synthesis of (R)-10-hydroxystearic acid. Accordingly, the hydration of oleic acid (up to 50 g/L) is performed on a multigram scale using the recombinant hydratase and FADH₂ generated in situ as cofactor. The produced (R)-10-hydroxystearic acid (ee > 97%) precipitates from the reaction solvent (water/glycerol/ethanol) and is conveniently recovered by simple filtration (>90% yield).

In this work, we describe a study on the biotransformation of seven natural occurring apocarotenoids by means of eleven selected fungal species. The substrates, namely ionone (α-, β- and γ-isomers), 3,4-dehydroionone, damascone (α- and β-isomers) and theaspirane are relevant flavour and fragrances components. We found that most of the investigated biotransformation reactions afforded oxidized products such as hydroxy- keto- or epoxy-derivatives. On the contrary, the reduction of the keto groups or the reduction of the double bond functional groups were observed only for few substrates, where the reduced products are however formed in minor amount. When starting apocarotenoids are isomers of the same chemical compound (e.g., ionone isomers) their biotransformation can give products very different from each other, depending both on the starting substrate and on the fungal species used. Since the majority of the starting apocarotenoids are often available in natural form and the described products are natural compounds, identified in flavours or fragrances, our biotransformation procedures can be regarded as prospective processes for the preparation of high value olfactory active compounds.