scholarly journals Characterization of the Jomthonic Acids Biosynthesis Pathway and Isolation of Novel Analogues in Streptomyces caniferus GUA-06-05-006A

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 259 ◽  
Author(s):  
Raúl García-Salcedo ◽  
Rubén Álvarez-Álvarez ◽  
Carlos Olano ◽  
Librada Cañedo ◽  
Alfredo Braña ◽  
...  
Keyword(s):  
Natural Products ◽  
Streptomyces Coelicolor ◽  
Transcriptional Unit ◽  
Constitutive Promoter ◽  
Biosynthesis Pathway ◽  
Marine Actinobacteria ◽  
Peptide Synthetase ◽  
Streptomyces Albus ◽  
Streptomyces Albus J1074

Jomthonic acids (JAs) are a group of natural products (NPs) with adipogenic activity. Structurally, JAs are formed by a modified β-methylphenylalanine residue, whose biosynthesis involves a methyltransferase that in Streptomyces hygroscopicus has been identified as MppJ. Up to date, three JA members (A–C) and a few other natural products containing β-methylphenylalanine have been discovered from soil-derived microorganisms. Herein, we report the identification of a gene (jomM) coding for a putative methyltransferase highly identical to MppJ in the chromosome of the marine actinobacteria Streptomyces caniferus GUA-06-05-006A. In its 5’ region, jomM clusters with two polyketide synthases (PKS) (jomP1, jomP2), a nonribosomal peptide synthetase (NRPS) (jomN) and a thioesterase gene (jomT), possibly conforming a single transcriptional unit. Insertion of a strong constitutive promoter upstream of jomP1 led to the detection of JA A, along with at least two novel JA family members (D and E). Independent inactivation of jomP1, jomN and jomM abolished production of JA A, JA D and JA E, indicating the involvement of these genes in JA biosynthesis. Heterologous expression of the JA biosynthesis cluster in Streptomyces coelicolor M1152 and in Streptomyces albus J1074 led to the production of JA A, B, C and F. We propose a pathway for JAs biosynthesis based on the findings here described.

scholarly journals Reconstruction of a Genome-Scale Metabolic Model of Streptomyces albus J1074: Improved Engineering Strategies in Natural Product Synthesis

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 304
Author(s):  
Cheewin Kittikunapong ◽  
Suhui Ye ◽  
Patricia Magadán-Corpas ◽  
Álvaro Pérez-Valero ◽  
Claudio J. Villar ◽  
...  
Keyword(s):  
Natural Products ◽  
De Novo ◽  
Streptomyces Coelicolor ◽  
Metabolic Model ◽  
Streptomyces Species ◽  
Model Driven ◽  
A Genome ◽  
Streptomyces Albus ◽  
Genome Scale ◽  
Streptomyces Albus J1074

Streptomyces albus J1074 is recognized as an effective host for heterologous production of natural products. Its fast growth and efficient genetic toolbox due to a naturally minimized genome have contributed towards its advantage in expressing biosynthetic pathways for a diverse repertoire of products such as antibiotics and flavonoids. In order to develop precise model-driven engineering strategies for de novo production of natural products, a genome-scale metabolic model (GEM) was reconstructed for the microorganism based on protein homology to model species Streptomyces coelicolor while drawing annotated data from databases and literature for further curation. To demonstrate its capabilities, the Salb-GEM was used to predict overexpression targets for desirable compounds using flux scanning with enforced objective function (FSEOF). Salb-GEM was also utilized to investigate the effect of a minimized genome on metabolic gene essentialities in comparison to another Streptomyces species, S. coelicolor.

scholarly journals العلاقة المظهرية والجينية لانواع جنس Streptomyces spp. المعزولة من الترب الملوثة بالهيدروكاربونات

2017 ◽  
Vol 11 (2) ◽  
pp. 62-69
Author(s):  
Esraa Gh. Al-Sammak
Keyword(s):  
Maximum Likelihood ◽  
Maximum Likelihood Method ◽  
Streptomyces Coelicolor ◽  
Likelihood Method ◽  
Simple Matching Coefficient ◽  
Streptomyces Spp ◽  
Streptomyces Albus ◽  
Streptomyces Albus J1074

يهدف البحث الى تسليط الضوء على دور التصنيف المتعدد Polyphasic والذي يضم كل من التصنيف المظهري والجيني لتحديد وتثبيت صفات النوع ضمن جنس الـStreptomyces   الصعب التصنيف نتيجة كثرة الانواع والتغاير الكبير في الصفات المظهرية اضافة لدورها في مجالات عدة منها البيئة من خلال تحملها العديد من املاح العناصرالثقيلة الموجودة في البيئات الملوثة بالهيدروكاربونات واشتراكها في التخلص من الملوثات. تم عزل وتشخيص ست  عزلات من البكتريا الخيطية  التابعة لجنس Streptomyces من عشرين عينة تربة ملوثة بالهيدروكاربونات وترب حدائق .  شخصت الى ثلاثة انواع اعتمادا على دراسة الصفات المظهرية والجينية من خلال دراسة تتابع جزء الـ16SrDNA باستخدام البادئ 27f  و 1392r  وشخصت سلالتين على انها تابعة للنوع     Streptomyces flavogriseus ATCC 33331 وسلالتين للنوع Streptomyces coelicolor A3(2) واخيرا سلالتين تابعة للنوع  Streptomyces albus J1074  . اعتمادا على الصفات المظهرية والبالغة 48 صفة  و باستخدام التصنيف العددي والربط باستخدام المعدل الموزون و معامل التشابه البسيط Simple matching coefficient (Ssm)  باستخدام البرنامج الاحصائي SPSS  , تعنقدت السلالات في ثلاثة عناقيد ضمن المخطط الشجري ضم  العنقود A سلالتين للنوعStreptomyces coelicolor   مرتبطة عند نسبة تشابه 99%  في حين تعنقدت سلالتي النوع Streptomyces albus  ضمن العنقود B  وعند نسبة تشابه 95% كما تعنقدت سلالتي النوع Streptomyces flavogriseus  ضمن العنقود C  وبنسبة تشابه 95% . اظهرت الانواع المعزولة مستعمرات طباشيرية رصاصية الى بيضاء وتميز الغزل الهوائي للنوع   Streptomyces albus بكونه حلزوني مكبوس متفرع وكثيف في حين تميز بكون خيوط الغزل الهوائي متعرج وغير متفرع للنوع  Streptomyces flavogriseus وظهر الغزل الهوائي للنوع  Streptomyces coelicolor متفرع متحلزن ومتعرج و جميعها منتجة لرائحة  التربة. اظهرت جميع الانواع قيد الدراسة حساسية  لاملاح كل من كلوريد وكبريتات الزئبق , في حين اظهرت جميع الانواع مقاومة لكل من كلوريد ونترات الكوبلت و كبريتات الزنك و نترات  وخلات الرصاص و كبريتات النيكل و خلات الفضة وثنائي اوكسيد التيتانيوم . اعطت جميع الانواع حساسية للمضاد الحيوي,Ciprofloxacin  10 مايكروغرام  , 10 Tobramycinمايكروغرام  ,  Gentamicin  10 مايكروغرام , Vancomycin 30 مايكروغرام , Amikacin10مايكروغرام, Imipenem 10مايكروغرام. كما  تعنقدت الانواع ايضا عند استخدام التصنيف الجيني الى ثلاثة عناقيد  ضمن الشجرة  التطورية وبنسب تشابه تراوحت بين  96.7- 99.4  %باستخدام  Clustal W  وطريقة maximum likelihood method  باستخدام برنامج Mega 5.

scholarly journals Elucidation of the genetic mechanisms contributing to moenomycin resistance in actinobacteria

2018 ◽  
Vol 22 ◽  
pp. 203-209
Author(s):  
B. O. Ostash ◽  
O. S. Yushchuk ◽  
O. T. Koshla ◽  
Y. Rebets ◽  
I. S. Ostash ◽  
...  
Keyword(s):  
Cell Wall ◽  
Streptomyces Coelicolor ◽  
Molecular Genetic ◽  
Resistance Mechanisms ◽  
Genus Streptomyces ◽  
Streptomyces Albus ◽  
Genetic Mechanisms ◽  
Peptidoglycan Glycosyltransferases ◽  
Streptomyces Albus J1074 ◽  
Model Strain

Aim. Moenomycins are phosphoglycolipid antibiotics produced almost exclusively by representatives of genus Streptomyces. These antibiotics directly inhibit peptidoglycan glycosyltransferases and are extremely active against cocci. Here we studied how antibiotic-producing actinobacteria protect themselves from toxic action of moenomycins. Methods. Microbiological and molecular genetic approaches were combined to reveal intrinsic levels and distribution of moenomycin resistance across actinobacteria genera, and to pinpoint genes contributing to moenomycin resistance in model strain Streptomyces coelicolor M145. Results. Out of 51 actinobacterial species (90 % of which Streptomyces) being tested, only Streptomyces albus J1074 turned out to be highly susceptible to moenomycin A, although resistant variants can be facilely raised. Several classes of mutations increased level of susceptibility of S. coelicolor to moenomycin, although in no case the latter was equal to what we observed in J1074 strain. Conclusions. Moenomycin resistance is widespread across actinobacteria, and it most likely is caused by a combination factors, such as richly decorated cell wall and organization of divisome apparatus. It is possible that moenomycin resistance mechanisms operating in actinobacteria and pathogenic cocci are different. Keywords: moenomycin, antibiotic resistance, peptidoglycan.

scholarly journals New insights into paulomycin biosynthesis pathway in Streptomyces albus J1074 and generation of novel derivatives by combinatorial biosynthesis

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Aránzazu González ◽  
Miriam Rodríguez ◽  
Alfredo F. Braña ◽  
Carmen Méndez ◽  
José A. Salas ◽  
...  
Keyword(s):  
Combinatorial Biosynthesis ◽  
Biosynthesis Pathway ◽  
Streptomyces Albus ◽  
Streptomyces Albus J1074

scholarly journals Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Song Meng ◽  
Andrew D. Steele ◽  
Wei Yan ◽  
Guohui Pan ◽  
Edward Kalkreuter ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Assembly Line ◽  
Polyketide Synthase ◽  
Genome Mining ◽  
Assembly Lines ◽  
Biologically Relevant ◽  
Peptide Synthetase ◽  
Adenosyl Methionine

AbstractNature forms S-S bonds by oxidizing two sulfhydryl groups, and no enzyme installing an intact hydropersulfide (-SSH) group into a natural product has been identified to date. The leinamycin (LNM) family of natural products features intact S-S bonds, and previously we reported an SH domain (LnmJ-SH) within the LNM hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line as a cysteine lyase that plays a role in sulfur incorporation. Here we report the characterization of an S-adenosyl methionine (SAM)-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin (GNM) biosynthesis, discovery of hydropersulfides as the nascent products of the GNM and LNM hybrid NRPS-PKS assembly lines, and revelation of three SH domains (GnmT-SH, LnmJ-SH, and WsmR-SH) within the GNM, LNM, and weishanmycin (WSM) hybrid NRPS-PKS assembly lines as thiocysteine lyases. Based on these findings, we propose a biosynthetic model for the LNM family of natural products, featuring thiocysteine lyases as PKS domains that directly install a -SSH group into the GNM, LNM, or WSM polyketide scaffold. Genome mining reveals that SH domains are widespread in Nature, extending beyond the LNM family of natural products. The SH domains could also be leveraged as biocatalysts to install an -SSH group into other biologically relevant scaffolds.

scholarly journals Characterization of SafC, a Catechol 4-O-Methyltransferase Involved in Saframycin Biosynthesis

2007 ◽  
Vol 73 (11) ◽  
pp. 3575-3580 ◽  
Author(s):  
James T. Nelson ◽  
Jaeheon Lee ◽  
James W. Sims ◽  
Eric W. Schmidt
Keyword(s):  
Escherichia Coli ◽  
Natural Products ◽  
Caffeic Acid ◽  
Antitumor Agents ◽  
Myxococcus Xanthus ◽  
Clinical Development ◽  
Nonribosomal Peptide Synthetase ◽  
Biotechnological Potential ◽  
Peptide Synthetase

ABSTRACT Members of the saframycin/safracin/ecteinascidin family of peptide natural products are potent antitumor agents currently under clinical development. Saframycin MX1, from Myxococcus xanthus, is synthesized by a nonribosomal peptide synthetase, SafAB, and an O-methyltransferase, SafC, although other proteins are likely involved in the pathway. SafC was overexpressed in Escherichia coli, purified to homogeneity, and assayed for its ability to methylate a variety of substrates. SafC was able to catalyze the O-methylation of catechol derivatives but not phenols. Among the substrates tested, the best substrate for SafC was l-dihydroxyphenylalanine (l-dopa), which was methylated specifically in the 4′-O position (k cat/Km = 5.5 × 103 M−1 s−1). SafC displayed less activity on other catechol derivatives, including catechol, dopamine, and caffeic acid. The more labile l-5′-methyldopa was an extremely poor substrate for SafC (k cat/Km = ∼2.8 × 10−5 M−1 s−1). l-Dopa thioester derivatives were also much less reactive than l-dopa. These results indicate that SafC-catalyzed 4′-O-methylation of l-dopa occurs prior to 5′-C-methylation, suggesting that 4′-O-methylation is likely the first committed step in the biosynthesis of saframycin MX1. SafC has biotechnological potential as a methyltransferase with unique regioselectivity.

scholarly journals Structural characterization of three noncanonical NTF2-like superfamily proteins: implications for polyketide biosynthesis

2020 ◽  
Vol 76 (8) ◽  
pp. 372-383
Author(s):  
Nemanja Vuksanovic ◽  
Xuechen Zhu ◽  
Dante A. Serrano ◽  
Vilja Siitonen ◽  
Mikko Metsä-Ketelä ◽  
...  
Keyword(s):  
Natural Products ◽  
Structural Characterization ◽  
Unknown Function ◽  
Biosynthetic Pathway ◽  
Streptomyces Coelicolor ◽  
Biosynthetic Pathways ◽  
Polyketide Biosynthesis ◽  
X Ray ◽  
Bona Fide

Proteins belonging to the NTF2-like superfamily are present in the biosynthetic pathways of numerous polyketide natural products, such as anthracyclins and benzoisochromanequinones. Some have been found to be bona fide polyketide cyclases, but many of them have roles that are currently unknown. Here, the X-ray crystal structures of three NTF2-like proteins of unknown function are reported: those of ActVI-ORFA from Streptomyces coelicolor A3(2) and its homologs Caci_6494, a protein from an uncharacterized biosynthetic cluster in Catenulispora acidiphila, and Aln2 from Streptomyces sp. CM020, a protein in the biosynthetic pathway of alnumycin. The presence of a solvent-accessible cavity and the conservation of the His/Asp dyad that is characteristic of many polyketide cyclases suggest a potential enzymatic role for these enzymes in polyketide biosynthesis.

scholarly journals Salumycin, a New Pyrazolequinone from a Streptomyces albus J1074 Mutant Strain

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4098
Author(s):  
Kaixiang Tao ◽  
Taijia Ye ◽  
Mingming Cao ◽  
Xiaolu Meng ◽  
Yuqing Li ◽  
...  
Keyword(s):  
Natural Products ◽  
Mutant Strain ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
X Ray Diffraction ◽  
Nmr Data ◽  
Streptomyces Albus ◽  
Infrared Spectrometer ◽  
Dpph Radical Scavenging ◽  
Streptomyces Albus J1074

Heterocyclic natural products with various bioactivities play significant roles in pharmaceuticals. Here, we isolated a heterocyclic compound salumycin (1) from a Streptomyces albus J1074 mutant strain. The structure of (1) was elucidated via single-crystal X-ray diffraction, mass spectrometry (MS), fourier transform infrared spectrometer (FTIR), and nuclear magnetic resonance (NMR) data analysis. Salumycin (1) contained a novel pyrazolequinone ring, which had never been previously reported in a natural product. Salumycin (1) exhibited moderate 2,2′-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging activity (EC50 = 46.3 ± 2.2 μM) compared with tert-butylhydroquinone (EC50 = 4.7 ± 0.3 μM). This study provides a new example of discovering novel natural products from bacteria.

scholarly journals Prototyping a valinomycin biosynthesis pathway within a cell-free transcription-translation (TX-TL) system

2016 ◽  
Author(s):  
Tiffany Zhou
Keyword(s):  
Escherichia Coli ◽  
Natural Products ◽  
Model Organism ◽  
New Drugs ◽  
Test Case ◽  
Biosynthesis Pathway ◽  
Genetic Pathways ◽  
Anticancer Effects ◽  
A Cell

1AbstractMany natural metabolites have antibacterial, antiviral, or anticancer effects and can be developed into new drugs. However, working with the microorganisms that produce these products can be challenging since they are not as well characterized as a model organism like Escherichia coli. In this paper, we investigate the potential for a cell-free transcription-translation (TX-TL) system to provide a rapid prototyping platform for characterizing new genetic pathways. We use the valinomycin biosynthesis pathway as a test case, and we show successful heterologous expression of the heterodimeric valinomycin synthetase (VlmSyn, Vlm1: 374 kDa and Vlm2: 284 kDa) from Strep-tomyces tsusimaensis within the TX-TL system. Using LC-MS analysis, we find that valinomycin is produced at low but detectable levels, even when only one out of the three basic precursors is fed into the system. Our work represents another step towards applying cell-free biosynthesis to the discovery and characterization of new natural products.

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