Unusual Activities of the Thioesterase Domain for the Biosynthesis of the Polycyclic Tetramate Macrolactam HSAF in <i>Lysobacter enzymogenes</i> C3

Lou, Lili; Chen, Haotong; Cerny, Ronald L.; Li, Yaoyao; Shen, Yuemao; Du, Liangcheng

doi:10.1021/bi2015025

Cited by 39 publications

(41 citation statements)

References 32 publications

(57 reference statements)

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“…[13] A subsequent in vitro study has confirmed that the single HSAF NRPS module can accept two acyl chains to make two amide bonds with the a-and the d-amino groups of lornithine, respectively, forming the tetramate ring by a Dieckmann-type reaction. [12] In addition, the unusual dual activities of both a protease and a peptide ligase for the HSAF thioesterase (TE) domain, [14] and the tailoring enzymes for hydroxylations of both frontalamides and HSAF have been described. [5,15] However, it remains unclear how the polycycles in PTMs are formed after release of the nascent product from the PKS/NRPS assembly line.…”

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confidence: 99%

Mechanistic Insights into Polycycle Formation by Reductive Cyclization in Ikarugamycin Biosynthesis

Zhang

et al. 2014

Angewandte Chemie

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Ikarugamycin is a member of the polycyclic tetramate macrolactams (PTMs) family of natural products with diverse biological activities. The biochemical mechanisms for the formation of polycyclic ring systems in PTMs remain elusive. The enzymatic mechanism of constructing an inner five-membered ring in ikarugamycin is reported. A three-genecassette ikaABC from the marine-derived Streptomyces sp. ZJ306 is sufficient for conferring ikarugamycin production in a heterologous host. IkaC catalyzes a reductive cyclization reaction to form the inner five-membered ring by a Michael addition-like reaction. This study provides the first biochemical evidence for polycycle formation in PTMs and suggests a reductive cyclization strategy which may be potentially applicable in general to the corresponding ring formation in other PTMs.

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confidence: 99%

Mechanistic Insights into Polycycle Formation by Reductive Cyclization in Ikarugamycin Biosynthesis

Zhang

et al. 2014

Angewandte Chemie

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“…[1][2][3][4] This bacterial metabolite belongs to polycyclic tetramate macrolactams (PTM) that are emerging as a new class of natural products with distinct structural features. [5,6] HSAF exhibits a potent antifungal activity and shows a novel mode of action.…”

Section: Hsaf (1) Was Isolated From the Biocontrol Agent Lysobacter Ementioning

confidence: 99%

“…[5,6] HSAF exhibits a potent antifungal activity and shows a novel mode of action. [1][2][3][4] The HSAF biosynthetic gene cluster contains only a single-module hybrid polyketide synthasenonribosomal peptide synthetase (PKS-NRPS), although the PTM scaffold is apparently derived from two separate hexaketide chains and an ornithine residue. [1][2][3][4] This suggests that the same PKS module would act not only iteratively, but also separately, in order to link the two hexaketide chains with the NRPS-activated ornithine to form the characteristic PTM scaffold.…”

Section: Hsaf (1) Was Isolated From the Biocontrol Agent Lysobacter Ementioning

confidence: 99%

“…[1][2][3][4] The HSAF biosynthetic gene cluster contains only a single-module hybrid polyketide synthasenonribosomal peptide synthetase (PKS-NRPS), although the PTM scaffold is apparently derived from two separate hexaketide chains and an ornithine residue. [1][2][3][4] This suggests that the same PKS module would act not only iteratively, but also separately, in order to link the two hexaketide chains with the NRPS-activated ornithine to form the characteristic PTM scaffold. Recently, the Gulder group reported heterologous expression of the ikarugamycin (4) biosynthetic gene cluster in E. coli, [7] and the Zhang group reported the enzymatic mechanism for formation of the inner 5-memebered ring and demonstrated the polyketide origin of the ikarugamycin skeleton.…”

Section: Hsaf (1) Was Isolated From the Biocontrol Agent Lysobacter Ementioning

confidence: 99%

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Iterative Assembly of Two Separate Polyketide Chains by the Same Single‐Module Bacterial Polyketide Synthase in the Biosynthesis of HSAF

Chen

Ding

et al. 2014

Angewandte Chemie

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Antifungal HSAF (heat‐stable antifungal factor, dihydromaltophilin) is a polycyclic tetramate macrolactam from the biocontrol agent Lysobacter enzymogenes. Its biosynthetic gene cluster contains only a single‐module polyketide synthase–nonribosomal peptide synthetase (PKS‐NRPS), although two separate hexaketide chains are required to assemble the skeleton. To address the unusual biosynthetic mechanism, we expressed the biosynthetic genes in two “clean” strains of Streptomyces and showed the production of HSAF analogues and a polyene tetramate intermediate. We then expressed the PKS module in Escherichia coli and purified the enzyme. Upon incubation of the enzyme with acyl‐coenzyme A and reduced nicotinamide adenine dinucleotide phosphate (NADPH), a polyene was detected in the tryptic acyl carrier protein (ACP). Finally, we incubated the polyene–PKS with the NRPS module in the presence of ornithine and adenosine triphosphate (ATP), and we detected the same polyene tetramate as that in Streptomyces transformed with the PKS‐NRPS alone. Together, our results provide evidence for an unusual iterative biosynthetic mechanism for bacterial polyketide–peptide natural products.

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“…strain OC7 isolated from onshore sites was found to carry carbasol (CAR) -degrading genes (Maeda et al, 2010). Lysobacter was, recently, of great interest for taxonomical research as well as for bioremediation technologies and industrial applications (Zhang et al, 2011;Lou et al, 2012;Brito et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Decolorization of two azo dyes using marine Lysobacter sp. T312D9

Khouloud¹

2013

MJM

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Aims: Novel azo dye-degrading bacterium T312D9 strain has been isolated from Abou Quir Gulf, Alexandria, Egypt. Methodology and Results:The identification of the isolate by 16S rRNA gene sequencing revealed to be Lysobacter sp. This marine ecofriendly isolate was exploited for its ability to degrade two synthetic azo dyes considered as detrimental pollutants from industrial effluents: congo red and methyl red. Using different dye concentrations showed the highest metabolic activity for complete degradation obtained from 100 to 500 mg/L within 30 h under static condition, also, sustaining higher dye loading of 1 g/L was carried out. The significant induction of enzymes NADH -2,6-dichloroindophenol (NADH-DCIP) reductase and tyrosinase indicated their prominent role in dye degradation. The biodegradation of two azo dyes were analyzed by gas chromatographicmass spectrum analysis (GC-MS) and Fourier transform infrared spectroscopy (FTIR) before and after treatment. Toxicity study revealed the much less toxic nature of the metabolites produced after complete decolorization. Conclusion, significance and impact of study: Lysobacter sp T312D9 represent an inexpensive and promising marine bacteria for removal of both methyl and congo red. High sustainable metabolic activity for biodegradation under static condition. NADH-DCIP reductase and tyrosinase were significantly induced during biodegradation of dyes. The obtained metabolites revealed to be less toxic in nature which offers a practical biological treatment.

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Unusual Activities of the Thioesterase Domain for the Biosynthesis of the Polycyclic Tetramate Macrolactam HSAF in Lysobacter enzymogenes C3

Cited by 39 publications

References 32 publications

Mechanistic Insights into Polycycle Formation by Reductive Cyclization in Ikarugamycin Biosynthesis

Mechanistic Insights into Polycycle Formation by Reductive Cyclization in Ikarugamycin Biosynthesis

Iterative Assembly of Two Separate Polyketide Chains by the Same Single‐Module Bacterial Polyketide Synthase in the Biosynthesis of HSAF

Decolorization of two azo dyes using marine Lysobacter sp. T312D9

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