Synthesis Of Amino Acid Precursors Research Articles

Catabolism of phenylacetic acid in Penicillium rubens. Proteome-wide analysis in response to the benzylpenicillin side chain precursor

Biosynthesis of benzylpenicillin in filamentous fungi (e.g. Penicillium chrysogenum - renamed as Penicillium rubens- and Aspergillus nidulans) depends on the addition of CoA-activated forms of phenylacetic acid to isopenicillin N. Phenylacetic acid is also detoxified by means of the homogentisate pathway, which begins with the hydroxylation of phenylacetic acid to 2-hydroxyphenylacetate in a reaction catalysed by the pahA-encoded phenylacetate hydroxylase. This catabolic step has been tested in three different penicillin-producing strains of P. rubens (P. notatum, P. chrysogenum NRRL 1951 and P. chrysogenum Wisconsin 54–1255) in the presence of sucrose and lactose as non-repressing carbon sources. P. chrysogenum Wisconsin 54–1255 was able to accumulate 2-hydroxyphenylacetate at late culture times. Analysis of the P. rubens genome showed the presence of several PahA homologs, but only Pc16g01770 was transcribed under penicillin production conditions. Gene knock-down experiments indicated that the protein encoded by Pc16g01770 seems to have residual activity in phenylacetic acid degradation, this catabolic activity having no effect on benzylpenicillin biosynthesis. Proteome-wide analysis of the Wisconsin 54–1255 strain in response to phenylacetic acid revealed that this molecule has a positive effect on some proteins directly related to the benzylpenicillin biosynthetic pathway, the synthesis of amino acid precursors and other important metabolic processes. SignificanceThe adaptive response of Penicillium rubens to benzylpenicillin production conditions remains to be fully elucidated. This article provides important information about the molecular mechanisms interconnected with phenylacetate (benzylpenicillin side chain precursor) utilization and penicillin biosynthesis, and will contribute to the understanding of the complex physiology and adaptation mechanisms triggered by P. rubens (P. chrysogenum Wisconsin 54–1255) under benzylpenicillin production conditions.

Chiral Sugars Drive Enantioenrichment in Prebiotic Amino Acid Synthesis.

Chiral pentose sugars mediate the enantioselective synthesis of amino acid precursors, with the magnitude of the chiral induction dictated by a subtle cooperativity between sugar hydroxyl groups. Ribose and lyxose give opposite chiral preferences, and theoretical calculations reveal the pseudoenantiomeric nature of transition state structures from the two sugars. Prebiotically plausible mixtures of natural d-sugars lead to enantioenrichment of natural l-amino acid precursors. Temporal monitoring and kinetic modeling of the reaction reveal an unusual dynamic kinetic resolution that shifts toward an enantioselective pathway over time, providing an amplification mechanism for the transfer of chiral information. This work adds to growing evidence for synergy in the etiology of the single chirality of the two most important classes of biological molecules, the sugars that make up DNA and RNA and the amino acids that form proteins.

One-pot synthesis of amino acid precursors with insoluble organic matter in planetesimals with aqueous activity.

The exogenous delivery of organic molecules could have played an important role in the emergence of life on the early Earth. Carbonaceous chondrites are known to contain indigenous amino acids as well as various organic compounds and complex macromolecular materials, such as the so-called insoluble organic matter (IOM), but the origins of the organic matter are still subject to debate. We report that the water-soluble amino acid precursors are synthesized from formaldehyde, glycolaldehyde, and ammonia with the presence of liquid water, simultaneously with macromolecular organic solids similar to the chondritic IOM. Amino acid products from hydrothermal experiments after acid hydrolysis include α-, β-, and γ-amino acids up to five carbons, for which relative abundances are similar to those extracted from carbonaceous chondrites. One-pot aqueous processing from simple ubiquitous molecules can thus produce a wide variety of meteoritic organic matter from amino acid precursors to macromolecular IOM in chondrite parent bodies.

Synthesis of amino acid precursors from simulated interstellar media by high‐energy particles or photons

AbstractExtraterrestrial organic compounds have been considered as important sources for the origin of life on the Earth. In order to study the formation of organic compounds found in extraterrestrial bodies, simulated interstellar media were irradiated with high‐energy particles or photons. Particles used were protons from a Van de Graaff accelerator, protons and helium ions from a cyclotron, electrons from a synchrotron, and heavy ions from the “HIMAC” heavy ion accelerator. Photons used were UV light and soft X‐rays from a synchrotron. Gamma‐ray irradiation was performed by using a 60Co source. Amino acid precursors were formed from a mixture of carbon monoxide (or methodanol), ammonia (or nitrogen), and water by high‐energy particles, gamma rays, or X‐rays. If nitrogen molecule was used as N‐source, amino acid precursors could be formed by high‐energy particles, X‐rays and gamma rays, but not by UV light. When ammonia was used, amino acid precursors were detected in all cases, but energy yields (G‐values) of amino acid precursors by high‐energy particles were much higher than those by UV or X‐rays photons. Possible formation of amino acid precursors in interstellar environments was discussed from the point of view of chemical evolution toward origins of life. © 2008 Wiley Periodicals, Inc. Electron Comm Jpn, 91(3): 15– 21, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10069

Asymmetric synthesis of amino acid precursors in interstellar complex organics by circularly polarized light

The asymmetric synthesis of amino acid precursors from complex organics have been performed. A gaseous mixture of carbon monoxide, ammonia and water (molecules which are among those identified in the interstellar medium) was irradiated with 3.0 MeV protons to obtain amino acid precursors within high-molecular-weight complex organics of up to 3000 Da. The amino acid precursor products synthesized were then irradiated with right (R-) or left (L-) ultraviolet circularly polarized light (UV–CPL) obtained from a synchrotron radiation (SR) source. Glycine was a predominant product, and number of chiral amino acids including alanine were identified following acid hydrolysis. R-UV–CPL preferentially produced d-alanine, while L-UV–CPL produced more l-alanine. Enantiomeric excesses (% D–% L) of +0.44% and −0.65% were obtained by R-UV–CPL and L-UV–CPL, respectively. These results imply that the origins of chirality in meteoritic amino acids could be accounted for by the formation of asymmetric amino acid precursors from extraterrestrial complex organics by CPL in space.

Synthesis of Amino Acid Precursors from Simulated Interstellar Media by High-Energy Particles or Photons

Extraterrestrial organic compounds have been considered as important sources for the origin of life on the Earth. In order to study the formation of organic compounds found in extraterrestrial bodies, simulated interstellar media were irradiated with high energy particles or photons. Particles used were protons from a van de Graaff accelerator, protons and helium ions from a cyclotron, electrons from a synchrotron, and heavy ions from “HIMAC heavy ion accelerator. Photons used were UV light and soft X-rays from a synchrotron. Gamma-rays irradiation was performed by using a 60Co source. Amino acid precursors were formed from a mixture of carbon monoxide (or methanol), ammonia (or nitrogen) and water by high-energy particles, gamma-rays, or X-rays. If nitrogen molecule was used as N-source, amino acid precursors could be formed by high energy particles, X-rays and gamma-rays, but not by UV light. In the case that ammonia was used, amino acid precursors were detected in all the cases, but energy yields (G-values) of amino acid precursors by high energy particles were much higher than those by UV or X-ray photons. Possible formation of amino acid precursors in interstellar environments was discussed from the point of view of chemical evolution toward origins of life.

Vinylsulfones as Nucleophiles and Michael Acceptors in the Same Step: Stereoselective Synthesis of Amino Acid Precursors

Several precursors of unnatural amino acids have been synthesized by addition of vinyl sulfones to an imine derived from (R)-glyceraldehyde. In these reactions the addition not only takes place in a stereoselective way, but a hydride transfer is also produced giving rise to the saturated sulfones and a new imine.

分析化学的手法による多成分系D-,L-アミノ酸の光学分割の精査とその限界

The separation of hydrolyzed chiral amino acids in multiple components, such as high-molecular-weight interstellar type complex organics, was verified to compare with meteoritic amino acids. Reversed-phase high-performance liquid chromatography (RP-HPLC) gave±0.34% (n = 7) regarding the standard deviation(σ) of enantiomeric excesses (%D-%L) of D, L-alanine in a hydrolyzed fraction of complex organics. The chiral separation of D, L-alanine by the RP-HPLC method might be more convenient than gas chromatograph combined with the mass spectrometry (GC/MS) method in asymmetric synthesis verification. Possible pathways for the asymmetric synthesis of amino acid precursors (not asymmetric photolysis of monomer amino acids) were considered in terms of the detection limit of statistically significant enantiomeric excesses.

Metabolism of [14C]glutamate and [14C]glutamine by the ectomycorrhizal fungus Paxillus involutus

To examine pathways of glutamate and glutamine metabolism in the ectomycorrhizal fungus Paxillus involutus, tracer kinetic experiments were performed using L-[U-14C]glutamate and L-[U-14C]glutamine and the enzyme inhibitors methionine sulfoximine (MSX), azaserine (AZA) and aminooxyacetate (AOA). When [14C]glutamate was supplied to fungal cultures, 25% of the radioactivity of the amino acid fraction was incorporated into glutamine after 5 min feeding, but MSX inhibited incorporation of 14C into glutamine by 85%, suggesting the rapid operation of glutamine synthetase. Conversely, when P. involutus was fed with [14C]glutamine, 46% of the label was found in glutamate within 30 min of feeding and AZA inhibited glutamate formation by 90%. Taken together, these data indicate that glutamate synthase (GOGAT) is the major enzyme of glutamine degradation. In addition, the strong inhibition of glutamine utilization by AOA indicates that glutamine catabolism in P. involutus might involve a transamination process as an alternative pathway to GOGAT for glutamine degradation. The high 14CO2 evolution shows that glutamate and glutamine are further actively consumed as respiratory substrates, being channelled through the tricarboxylic acid (TCA) cycle and oxidized as CO2. It appears that synthesis of amino acid precursors during TCA cycle operation is an essential step for aspartate and alanine synthesis through aminotransferase activities in P. involutus.

Evolution from amino acids: lunar occurrence of their precursors.

Review of the present state of experimentally based concepts of organic evolution from amino acids. Earlier studies of the synthesis of amino acid precursors from meteoritic material, lunar dust, and terrestrial lava are briefly summarized, and laboratory experiments in which polymers of amino acids were obtained either by direct heating of dry amino acids or by heating aqueous solutions of mixtures of amino acids are described. In particular, a process is described by which alpha-amino acids were made to react to form linear chains of proteinoids. It is concluded that a proteinoid microsystem was a common ancestor of all life on earth.