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  • Open Access Croatian
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia
  • Open Access Croatian
    Authors: 
    Čatić, Igor; Salopek Weber, D;
    Country: Croatia
  • Open Access Croatian
    Authors: 
    Sanja Jurković;
    Country: Croatia
  • Open Access English
    Authors: 
    Đ. Parac-Osterman; V. Đurašević; A. Sutlović;
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia

    Today's chemical and physical-chemical wastewater discoloration methods do not completely meet demands regarding degree of discoloration. In this paper discoloration was performed using Fenton (FeSO4 · 7 H2O + H2O2 + H2SO4) and Fenton-like (FeCl3 · 6 H2O + H2O2 + HCOOH) chemical methods and physical-chemical method of coagulation/flocculation (using poly-electrolyte (POEL) combining anion active coagulant (modified poly-acrylamides) and cationic flocculant (product of nitrogen compounds) in combination with adsorption on activated carbon. Suitability of aforementioned methods was investigated on reactive and acid dyes, regarding their most common use in the textile industry. Also, investigations on dyes of different chromogen (anthraquinone, phthalocyanine, azo and xanthene) were carried out in order to determine the importance of molecular spatial structure. Oxidative effect of Fenton and Fenton-like reagents resulted in decomposition of colored chromogen and high degree of discoloration. However, the problem is the inability of adding POEL in stechiometrical ratio (also present in physical-chemical methods), when the phenomenon of overdosing coagulants occurs in order to obtain a higher degree of discoloration, creating a potential danger of burdening water with POEL. Input and output water quality was controlled through spectrophotometric measurements and standard biological parameters. In addition, part of the investigations concerned industrial wastewaters obtained from dyeing cotton materials using reactive dye (C. I. Reactive Blue 19), a process that demands the use of vast amounts of electrolytes. Also, investigations of industrial wastewaters was labeled as a crucial step carried out in order to avoid serious misassumptions and false conclusions, which may arise if dyeing processes are only simulated in the laboratory. Današnje kemijske i fizikalno-kemijske metode obezbojavanja otpadnih voda ne zadovoljavaju u potpunosti zahtjeve vezane uz stupanj obezbojavanja. U ovom radu obezbojavanje se provodilo pomoću Fentonove kemijske metode (FeSO4· 7 H2O + H2O2 + H2SO4) i modificirane Fentonove kemijske metode (FeCl3 · 6 H2O+H2O2+ HCOOH), te pomoću fizikalno-kemijske metode upotrebom koagulanata/flokulanata (polielektrolita-POEL), koja kombinira anionski koagulant (modificirani poliakrilamid) i kationski flokulant (produkt dušikovih spojeva) uz adsorpciju na aktivnom ugljenu. Prihvatljivost opisanih metoda ispitivana je za reaktivna i kisela bojila, s obzirom na njihovu raširenu primjenu u tekstilnoj industriji. Također, provedena su ispitivanja na bojilima različitih kromogena (antrakinon, ftalocijanin, azo i ksanten) s ciljem određivanja važnosti prostorne strukture molekule. Oksidativno djelovanje Fentonovog i modificiranog Fentonovog postupka dovodi do razgradnje obojenog kromogena i visokog stupnja obezbojavanja. Međutim, ustanovljena je nemogućnost dodavanja POEL u stehiometrijskom odnosu (također prisutno kod modificiranog Fentonovog postupka), odnosno dodavanje koagulanata u suvišku kako bi se postigao viši stupanj obezbojavanja, što u konačnici dovodi do opterećenja voda POEL-ima. Kvaliteta vode na ulazu i izlazu kontrolirana je pomoću spektrofotometrijskih mjerenja i uobičajenih bioloških parametara. U prilog tome, dio ispitivanja bio je vezan za industrijske otpadne vode bojadisaone, u kojoj se pamučni materijal bojadisao bojilom C. I. Reactive Blue 19 i to tehnološkim postupkom koji zahtijeva uporabu velike količine elektrolita. Također, ispitivanje industrijskih otpadnih voda označeno je ključnim korakom izbjegavanja niza krivih pretpostavki i zaključaka, koji bi mogli nastati u slučaju laboratorijskog simuliranja procesa bojadisanja.

  • Open Access Croatian
    Authors: 
    M. Majić Renjo; L. Ćurković;
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia
  • Publication . Other literature type . Article . 2007
    Open Access Croatian
    Authors: 
    Maksić, Zvonimir; Vianello, Robert; Kovačević, Borislav;
    Publisher: Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI)
    Country: Croatia
    Project: MZOS | Broensted and Lewis acids... (098-0982933-2932)

    Problem kako mjeriti znanstvenu produktivnost, a posebice njezinu kvalitetu, jedno je od onih pitanja na koje nikada neæemo dobiti jednoznačan odgovor. Razlog tome je činjenica da se znanstvena izvrsnost ne može egzaktno definirati. To podsjeća na neke izuzetno vaÞne pojmove u kemiji, kao što su to aromatičnost, hibridizacija atomskih orbitala i kutna (Baeyerova) napetost molekula, koji su uzidani u temelje ovog znanstvenog polja. Nema sumnje da ovi efekti postoje, ali se nažalost ne mogu strogo definirati. Unatoć tome, razvijeni su približni modeli, koji dobro opisuju spomenute neuhvatljive, ali važne fenomene. Zbog toga pitanje na koje ćemo pokušati dati odgovor u ovom prilogu glasi: postoji li kriterij izvrsnosti koji je s jedne strane jednostavan i praktičan, a s druge strane daje dovoljno dobru informaciju o natprosjećnim rezultatima postignutim u određenom razdoblju?

  • Publication . Other literature type . 2014
    Open Access Croatian
    Authors: 
    I. Kisić;
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia
  • Publication . Other literature type . Article . 2019
    Open Access Croatian
    Authors: 
    Marica Ivanković; Leonard Bauer; Antonia Ressler; Anamarija Rogina; Maja Antunović; Hrvoje Ivanković;
    Country: Croatia

    Bone tissue engineering (BTE) is a fast growing field focused on the development of bioactive 3D porous scaffolds as temporary extracellular matrixes that support cell attachment, proliferation and differentiation, and stimulate bone tissue formation in vivo. Over more than ten years, our group has been devoted to developing new biomaterials and methods to prepare 3D porous scaffolds for BTE applications. The potential of natural porous structures such as marine skeletons, composite materials, and hydrogels based on biodegradable polymers and bioresorbable hydroxyapatite ceramics have been studied. In this paper, an overview of our research and main achievements, published in international scientific publications, is provided. This work is licensed under a Creative Commons Attribution 4.0 International License. Inženjerstvo koštanog tkiva brzorastuće je polje istraživanja usmjereno na razvoj bioaktivnih 3D poroznih nosača, kao privremenih izvanstaničnih matrica, koji podržavaju prianjanje, umnažanje i diferencijaciju stanica te potiču stvaranje koštanog tkiva in vivo. Više od deset godina istraživanja naše grupe posvećena su razvoju novih materijala i postupaka za pripravu 3D poroznih nosača za inženjerstvo koštanog tkiva. Kao mogući nosači istraživani su porozni skeleti morskih organizama te kompozitni materijali i hidrogelovi na temelju biorazgradljivih polimera i bioresorbirajuće hidroksiapatitne keramike. U ovom radu dan je prikaz naših istraživanja i glavnih postignuća, objavljenih u međunarodnim znanstvenim publikacijama. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna.

  • Publication . Article . 2007
    Open Access English
    Authors: 
    Zorc, B.; Butula, I.;
    Publisher: Croatian Society of Chemical Engineers

    In this paper, a review of reactions with benzotriazole as synthetic auxiliary is given. In contrast to most other azoles, benzotriazole reacts with phosgene in molar ratio 1:1 yielding carboxylic acid chloride (BtcCl, 1), which readily reacts with nucleophiles giving reactive compounds. These products can be easily transformed into carbamates, ureas, semicarbazides, carbazides, sulfonylureas, sulfonylcarbazides, nitroalkanic acid esters, etc. In addition, benzotriazole was used in the synthesis of various heterocyclic compounds: benzoxazine, kinazoline, triazinetrione, hydantoin and oxadiazine derivatives. The reaction of chloride 1 with amino acids enabled the use of benzotriazole in peptide chemistry, with triple role of benzotriazolecarbonyl group as N-protecting, N-activating, and both N-protecting/C-activating group. N-(1-benzotriazolecarbonyl)-amino acids 25 are starting compounds in the synthesis of various amino acid, di- and tripeptide derivatives, hydantoic acids and hydroxyureas.Benzotriazole was also applied in the preparation of polymer-drug and thiomer-drug conjugates, polymeric prodrugs with drugs covalently bound to the polymeric carriers. Such macromolecular prodrugs may offer many advantages compared to other drug delivery systems such as increased drug solubility, prolonged drug release, increased stability. It is also possible to accumulate the drug at the site of the pathological process and to minimize its toxicity. In this paper, the binding of drugs from various therapeutic groups (mostly nonsteroidal, anti-inflammatory drugs) to polymersof polyaspartamide type by the benzotriazolide method is described.

  • Open Access English
    Authors: 
    Zucko; J. ...(et al.); Starcevic, A.; Hranueli, D.;
    Publisher: Croatian Society of Chemical Engineers

    Polyketides and non-ribosomal peptides represent a large class of structurally diverse natural products much studied over recent years because the enzymes that synthesise them, the modular polyketide synthases (PKSs) and the non-ribosomal peptide synthetases (NRPSs), share striking architectural similarities that can be exploited to generate "un-natural" natural products. PKS and NRPS proteins are multifunctional, composed of a co-linear arrangement of discrete protein domains representing each enzymic activity needed for chain elongation using either carboxylic acid or amino acid building blocks. Each domain is housed within larger modules which form the complex. Polyketide and peptide antibiotics, antifungals, antivirals, cytostatics, immunosuppressants, antihypertensives, antidiabetics, antimalarials and anticholesterolemics are in clinical use. Of commercial importance are also polyketide and peptide antiparasitics, coccidiostatics,animal growth promoters and natural insecticides.Polyketides are assembled through serial condensations of activated coenzyme-A thioester monomers derived from simple organic acids such as acetate, propionate and butyrate. The choice of organic acid allows the introduction of different chiral centres into the polyketide backbone. The active sites required for condensation include an acyltransferase (AT), an acyl carrier protein (ACP) and a ß-ketoacylsynthase (KS). Each condensation results in a ß-keto group that undergoes all, some or none of a series of processing steps. Active sites that perform these reactions are contained within the following domains; ketoreductase (KR), dehydratase (DH) and an enoylreductase (ER). The absence of any ß-keto processing results in the incorporation of a ketone group into the growing polyketide chain, a KR alone gives rise to a hydroxyl moiety, a KR and DH produce an alkene, while the combination of KR, DH and ER domains lead to complete reduction to an alkane. Most often, the last module contains the thioesterase domain (TE) responsible for the release of linear polyketide chain from the enzyme and final cyclisation. After assembly, the polyketide backbone typically undergoes post-PKS modifications such as hydroxylation(s), methylation(s) and glycosylation(s) to give the final active compound.Non-ribosomal peptides are assembled by the so-called "multiple carrier thio-template mechanism". Three domains are necessary for an elongation module: an adenylation (A) domain that selects the substrate amino acid, analogous to a polyketide AT domain, and activates it as an amino acyl adenylate; a peptidyl carrier protein (PCP) that binds the co-factor 4-phosphopantetheine to which the activated amino acid is covalently attached, analogous to the ACP of a PKS; and a condensation (C) domain that catalyzes peptide bond formation, again analogous to the KS in modular PKSs. The NRPSs also contain a (Te) domain located at the C-terminal of the protein which is essential for release of linear, cyclic or branched cyclic peptides. Auxiliary activities can further enlarge the structural diversity of the peptide especially common are epimerization domains (Epim) that convert the thioester-bound amino acid from an L- to D- configuration.There has been a lot of interest in the last few years in generating new compounds for the production of novel drugs by manipulating the programming of such clusters in vitro (e.g. the idea of combinatorial biosynthesis). However, an important barrier to the progress is the fact that most changes made by in vitro methods result in very low yields or no detectable product. A possible solution to the yield problem would be the generation of novel clusters by homologous recombination in vivo, because this would favour more closely related sequences and should reduce problems caused by non-functional incompatible junctions.The Unified Modeling Language (UML) was used to define the platform independent integral generic program packages, CompGen and ClustScan, which are under development to model these processes in silico. The heart of CompGen is a specially structured database, based on BioSQL v1.29, which connects the biosynthetic order of synthase/synthetase enzymes to the sequences of the component polypeptides. The additional linkage to the gene sequences allows the integration of DNA sequence with product structure. The database contains sequences of the well-characterised PKS/NRPS clusters, and non-annotated sequenced clusters whose structure and functionis yet unknown, to act as building blocks for the production of novel products. It is easy to add custom sequences to the database and to annotate them by the use of propriety protein profiles designed by Pfam database and HMMER. One function of the program is the ability to generate virtual recombinants between clusters. This can be done using a recombination model (with optional parameters) to predict sites for homologous recombination or by user defined recombination sites (e.g. to model in vitro genetic manipulation such as module replacement). The program predicts the linear polyketide structure of the resulting "un-natural" natural products with a chemical description using isomeric SMILES. Molecular modelling of the subsequent spontaneous cyclisation process produces structures for a virtual compound database for further molecular modelling studies using PASS and CDD technology. An optional "reverse genetics" module analyses a given chemical structure to see if it could be produced by a novel PKS/NRPS synthesis cluster and suggests the DNA sequence of a suitable cluster based on building blocks derived from clusters contained in the database.Overall, the CompGen allows in silico generation of the database of novel "un-natural" natural chemical compounds that can be used for in silico screening using PASS or CDD technology. The other integral generic program package, ClustScan, will recognise and annotate new gene clusters from microbial genome sequencing projects or in metagenomes of soil and/or marine microorganisms.

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2,618 Research products, page 1 of 262
  • Open Access Croatian
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia
  • Open Access Croatian
    Authors: 
    Čatić, Igor; Salopek Weber, D;
    Country: Croatia
  • Open Access Croatian
    Authors: 
    Sanja Jurković;
    Country: Croatia
  • Open Access English
    Authors: 
    Đ. Parac-Osterman; V. Đurašević; A. Sutlović;
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia

    Today's chemical and physical-chemical wastewater discoloration methods do not completely meet demands regarding degree of discoloration. In this paper discoloration was performed using Fenton (FeSO4 · 7 H2O + H2O2 + H2SO4) and Fenton-like (FeCl3 · 6 H2O + H2O2 + HCOOH) chemical methods and physical-chemical method of coagulation/flocculation (using poly-electrolyte (POEL) combining anion active coagulant (modified poly-acrylamides) and cationic flocculant (product of nitrogen compounds) in combination with adsorption on activated carbon. Suitability of aforementioned methods was investigated on reactive and acid dyes, regarding their most common use in the textile industry. Also, investigations on dyes of different chromogen (anthraquinone, phthalocyanine, azo and xanthene) were carried out in order to determine the importance of molecular spatial structure. Oxidative effect of Fenton and Fenton-like reagents resulted in decomposition of colored chromogen and high degree of discoloration. However, the problem is the inability of adding POEL in stechiometrical ratio (also present in physical-chemical methods), when the phenomenon of overdosing coagulants occurs in order to obtain a higher degree of discoloration, creating a potential danger of burdening water with POEL. Input and output water quality was controlled through spectrophotometric measurements and standard biological parameters. In addition, part of the investigations concerned industrial wastewaters obtained from dyeing cotton materials using reactive dye (C. I. Reactive Blue 19), a process that demands the use of vast amounts of electrolytes. Also, investigations of industrial wastewaters was labeled as a crucial step carried out in order to avoid serious misassumptions and false conclusions, which may arise if dyeing processes are only simulated in the laboratory. Današnje kemijske i fizikalno-kemijske metode obezbojavanja otpadnih voda ne zadovoljavaju u potpunosti zahtjeve vezane uz stupanj obezbojavanja. U ovom radu obezbojavanje se provodilo pomoću Fentonove kemijske metode (FeSO4· 7 H2O + H2O2 + H2SO4) i modificirane Fentonove kemijske metode (FeCl3 · 6 H2O+H2O2+ HCOOH), te pomoću fizikalno-kemijske metode upotrebom koagulanata/flokulanata (polielektrolita-POEL), koja kombinira anionski koagulant (modificirani poliakrilamid) i kationski flokulant (produkt dušikovih spojeva) uz adsorpciju na aktivnom ugljenu. Prihvatljivost opisanih metoda ispitivana je za reaktivna i kisela bojila, s obzirom na njihovu raširenu primjenu u tekstilnoj industriji. Također, provedena su ispitivanja na bojilima različitih kromogena (antrakinon, ftalocijanin, azo i ksanten) s ciljem određivanja važnosti prostorne strukture molekule. Oksidativno djelovanje Fentonovog i modificiranog Fentonovog postupka dovodi do razgradnje obojenog kromogena i visokog stupnja obezbojavanja. Međutim, ustanovljena je nemogućnost dodavanja POEL u stehiometrijskom odnosu (također prisutno kod modificiranog Fentonovog postupka), odnosno dodavanje koagulanata u suvišku kako bi se postigao viši stupanj obezbojavanja, što u konačnici dovodi do opterećenja voda POEL-ima. Kvaliteta vode na ulazu i izlazu kontrolirana je pomoću spektrofotometrijskih mjerenja i uobičajenih bioloških parametara. U prilog tome, dio ispitivanja bio je vezan za industrijske otpadne vode bojadisaone, u kojoj se pamučni materijal bojadisao bojilom C. I. Reactive Blue 19 i to tehnološkim postupkom koji zahtijeva uporabu velike količine elektrolita. Također, ispitivanje industrijskih otpadnih voda označeno je ključnim korakom izbjegavanja niza krivih pretpostavki i zaključaka, koji bi mogli nastati u slučaju laboratorijskog simuliranja procesa bojadisanja.

  • Open Access Croatian
    Authors: 
    M. Majić Renjo; L. Ćurković;
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia
  • Publication . Other literature type . Article . 2007
    Open Access Croatian
    Authors: 
    Maksić, Zvonimir; Vianello, Robert; Kovačević, Borislav;
    Publisher: Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI)
    Country: Croatia
    Project: MZOS | Broensted and Lewis acids... (098-0982933-2932)

    Problem kako mjeriti znanstvenu produktivnost, a posebice njezinu kvalitetu, jedno je od onih pitanja na koje nikada neæemo dobiti jednoznačan odgovor. Razlog tome je činjenica da se znanstvena izvrsnost ne može egzaktno definirati. To podsjeća na neke izuzetno vaÞne pojmove u kemiji, kao što su to aromatičnost, hibridizacija atomskih orbitala i kutna (Baeyerova) napetost molekula, koji su uzidani u temelje ovog znanstvenog polja. Nema sumnje da ovi efekti postoje, ali se nažalost ne mogu strogo definirati. Unatoć tome, razvijeni su približni modeli, koji dobro opisuju spomenute neuhvatljive, ali važne fenomene. Zbog toga pitanje na koje ćemo pokušati dati odgovor u ovom prilogu glasi: postoji li kriterij izvrsnosti koji je s jedne strane jednostavan i praktičan, a s druge strane daje dovoljno dobru informaciju o natprosjećnim rezultatima postignutim u određenom razdoblju?

  • Publication . Other literature type . 2014
    Open Access Croatian
    Authors: 
    I. Kisić;
    Publisher: Croatian Society of Chemical Engineers
    Country: Croatia
  • Publication . Other literature type . Article . 2019
    Open Access Croatian
    Authors: 
    Marica Ivanković; Leonard Bauer; Antonia Ressler; Anamarija Rogina; Maja Antunović; Hrvoje Ivanković;
    Country: Croatia

    Bone tissue engineering (BTE) is a fast growing field focused on the development of bioactive 3D porous scaffolds as temporary extracellular matrixes that support cell attachment, proliferation and differentiation, and stimulate bone tissue formation in vivo. Over more than ten years, our group has been devoted to developing new biomaterials and methods to prepare 3D porous scaffolds for BTE applications. The potential of natural porous structures such as marine skeletons, composite materials, and hydrogels based on biodegradable polymers and bioresorbable hydroxyapatite ceramics have been studied. In this paper, an overview of our research and main achievements, published in international scientific publications, is provided. This work is licensed under a Creative Commons Attribution 4.0 International License. Inženjerstvo koštanog tkiva brzorastuće je polje istraživanja usmjereno na razvoj bioaktivnih 3D poroznih nosača, kao privremenih izvanstaničnih matrica, koji podržavaju prianjanje, umnažanje i diferencijaciju stanica te potiču stvaranje koštanog tkiva in vivo. Više od deset godina istraživanja naše grupe posvećena su razvoju novih materijala i postupaka za pripravu 3D poroznih nosača za inženjerstvo koštanog tkiva. Kao mogući nosači istraživani su porozni skeleti morskih organizama te kompozitni materijali i hidrogelovi na temelju biorazgradljivih polimera i bioresorbirajuće hidroksiapatitne keramike. U ovom radu dan je prikaz naših istraživanja i glavnih postignuća, objavljenih u međunarodnim znanstvenim publikacijama. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna.

  • Publication . Article . 2007
    Open Access English
    Authors: 
    Zorc, B.; Butula, I.;
    Publisher: Croatian Society of Chemical Engineers

    In this paper, a review of reactions with benzotriazole as synthetic auxiliary is given. In contrast to most other azoles, benzotriazole reacts with phosgene in molar ratio 1:1 yielding carboxylic acid chloride (BtcCl, 1), which readily reacts with nucleophiles giving reactive compounds. These products can be easily transformed into carbamates, ureas, semicarbazides, carbazides, sulfonylureas, sulfonylcarbazides, nitroalkanic acid esters, etc. In addition, benzotriazole was used in the synthesis of various heterocyclic compounds: benzoxazine, kinazoline, triazinetrione, hydantoin and oxadiazine derivatives. The reaction of chloride 1 with amino acids enabled the use of benzotriazole in peptide chemistry, with triple role of benzotriazolecarbonyl group as N-protecting, N-activating, and both N-protecting/C-activating group. N-(1-benzotriazolecarbonyl)-amino acids 25 are starting compounds in the synthesis of various amino acid, di- and tripeptide derivatives, hydantoic acids and hydroxyureas.Benzotriazole was also applied in the preparation of polymer-drug and thiomer-drug conjugates, polymeric prodrugs with drugs covalently bound to the polymeric carriers. Such macromolecular prodrugs may offer many advantages compared to other drug delivery systems such as increased drug solubility, prolonged drug release, increased stability. It is also possible to accumulate the drug at the site of the pathological process and to minimize its toxicity. In this paper, the binding of drugs from various therapeutic groups (mostly nonsteroidal, anti-inflammatory drugs) to polymersof polyaspartamide type by the benzotriazolide method is described.

  • Open Access English
    Authors: 
    Zucko; J. ...(et al.); Starcevic, A.; Hranueli, D.;
    Publisher: Croatian Society of Chemical Engineers

    Polyketides and non-ribosomal peptides represent a large class of structurally diverse natural products much studied over recent years because the enzymes that synthesise them, the modular polyketide synthases (PKSs) and the non-ribosomal peptide synthetases (NRPSs), share striking architectural similarities that can be exploited to generate "un-natural" natural products. PKS and NRPS proteins are multifunctional, composed of a co-linear arrangement of discrete protein domains representing each enzymic activity needed for chain elongation using either carboxylic acid or amino acid building blocks. Each domain is housed within larger modules which form the complex. Polyketide and peptide antibiotics, antifungals, antivirals, cytostatics, immunosuppressants, antihypertensives, antidiabetics, antimalarials and anticholesterolemics are in clinical use. Of commercial importance are also polyketide and peptide antiparasitics, coccidiostatics,animal growth promoters and natural insecticides.Polyketides are assembled through serial condensations of activated coenzyme-A thioester monomers derived from simple organic acids such as acetate, propionate and butyrate. The choice of organic acid allows the introduction of different chiral centres into the polyketide backbone. The active sites required for condensation include an acyltransferase (AT), an acyl carrier protein (ACP) and a ß-ketoacylsynthase (KS). Each condensation results in a ß-keto group that undergoes all, some or none of a series of processing steps. Active sites that perform these reactions are contained within the following domains; ketoreductase (KR), dehydratase (DH) and an enoylreductase (ER). The absence of any ß-keto processing results in the incorporation of a ketone group into the growing polyketide chain, a KR alone gives rise to a hydroxyl moiety, a KR and DH produce an alkene, while the combination of KR, DH and ER domains lead to complete reduction to an alkane. Most often, the last module contains the thioesterase domain (TE) responsible for the release of linear polyketide chain from the enzyme and final cyclisation. After assembly, the polyketide backbone typically undergoes post-PKS modifications such as hydroxylation(s), methylation(s) and glycosylation(s) to give the final active compound.Non-ribosomal peptides are assembled by the so-called "multiple carrier thio-template mechanism". Three domains are necessary for an elongation module: an adenylation (A) domain that selects the substrate amino acid, analogous to a polyketide AT domain, and activates it as an amino acyl adenylate; a peptidyl carrier protein (PCP) that binds the co-factor 4-phosphopantetheine to which the activated amino acid is covalently attached, analogous to the ACP of a PKS; and a condensation (C) domain that catalyzes peptide bond formation, again analogous to the KS in modular PKSs. The NRPSs also contain a (Te) domain located at the C-terminal of the protein which is essential for release of linear, cyclic or branched cyclic peptides. Auxiliary activities can further enlarge the structural diversity of the peptide especially common are epimerization domains (Epim) that convert the thioester-bound amino acid from an L- to D- configuration.There has been a lot of interest in the last few years in generating new compounds for the production of novel drugs by manipulating the programming of such clusters in vitro (e.g. the idea of combinatorial biosynthesis). However, an important barrier to the progress is the fact that most changes made by in vitro methods result in very low yields or no detectable product. A possible solution to the yield problem would be the generation of novel clusters by homologous recombination in vivo, because this would favour more closely related sequences and should reduce problems caused by non-functional incompatible junctions.The Unified Modeling Language (UML) was used to define the platform independent integral generic program packages, CompGen and ClustScan, which are under development to model these processes in silico. The heart of CompGen is a specially structured database, based on BioSQL v1.29, which connects the biosynthetic order of synthase/synthetase enzymes to the sequences of the component polypeptides. The additional linkage to the gene sequences allows the integration of DNA sequence with product structure. The database contains sequences of the well-characterised PKS/NRPS clusters, and non-annotated sequenced clusters whose structure and functionis yet unknown, to act as building blocks for the production of novel products. It is easy to add custom sequences to the database and to annotate them by the use of propriety protein profiles designed by Pfam database and HMMER. One function of the program is the ability to generate virtual recombinants between clusters. This can be done using a recombination model (with optional parameters) to predict sites for homologous recombination or by user defined recombination sites (e.g. to model in vitro genetic manipulation such as module replacement). The program predicts the linear polyketide structure of the resulting "un-natural" natural products with a chemical description using isomeric SMILES. Molecular modelling of the subsequent spontaneous cyclisation process produces structures for a virtual compound database for further molecular modelling studies using PASS and CDD technology. An optional "reverse genetics" module analyses a given chemical structure to see if it could be produced by a novel PKS/NRPS synthesis cluster and suggests the DNA sequence of a suitable cluster based on building blocks derived from clusters contained in the database.Overall, the CompGen allows in silico generation of the database of novel "un-natural" natural chemical compounds that can be used for in silico screening using PASS or CDD technology. The other integral generic program package, ClustScan, will recognise and annotate new gene clusters from microbial genome sequencing projects or in metagenomes of soil and/or marine microorganisms.

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