Functional Characterization of PyrG, an Unusual Nonribosomal Peptide Synthetase Module from the Pyridomycin Biosynthetic Pathway

ChemBioChem ◽  
2016 ◽  
Vol 17 (15) ◽  
pp. 1421-1425 ◽  
Author(s):  
Tingting Huang ◽  
Lili Li ◽  
Nelson L. Brock ◽  
Zixin Deng ◽  
Shuangjun Lin
Keyword(s):  
Biosynthetic Pathway ◽  
Functional Characterization ◽  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase

scholarly journals New Insight into the Ochratoxin A Biosynthetic Pathway through Deletion of a Nonribosomal Peptide Synthetase Gene in Aspergillus carbonarius

2012 ◽  
Vol 78 (23) ◽  
pp. 8208-8218 ◽  
Author(s):  
Antonia Gallo ◽  
Kenneth S. Bruno ◽  
Michele Solfrizzo ◽  
Giancarlo Perrone ◽  
Giuseppina Mulè ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Biosynthetic Pathway ◽  
Nonribosomal Peptide Synthetase ◽  
Gene Encoding ◽  
Nonribosomal Peptide ◽  
Content Type ◽  
Peptide Synthetase ◽  
Ochratoxin Α ◽  
Hydrolysis Of ◽  
Insight Into

ABSTRACTOchratoxin A (OTA), a mycotoxin produced byAspergillusandPenicilliumspecies, is composed of a dihydroisocoumarin ring linked to phenylalanine, and its biosynthetic pathway has not yet been completely elucidated. Most of the knowledge regarding the genetic and enzymatic aspects of OTA biosynthesis has been elucidated inPenicilliumspecies. InAspergillusspecies, onlypksgenes involved in the initial steps of the pathway have been partially characterized. In our study, the inactivation of a gene encoding a nonribosomal peptide synthetase (NRPS) in OTA-producingA. carbonariusITEM 5010 has eliminated the ability of this fungus to produce OTA. This is the first report on the involvement of annrpsgene product in OTA biosynthetic pathway in anAspergillusspecies. The absence of OTA and ochratoxin α, the isocoumaric derivative of OTA, and the concomitant increase of ochratoxin β, the dechloro analog of ochratoxin α, were observed in the liquid culture of transformed strain. The data provide the first evidence that the enzymatic step adding phenylalanine to polyketide dihydroisocoumarin precedes the chlorination step to form OTA inA. carbonariusand that ochratoxin α is a product of hydrolysis of OTA, giving an interesting new insight into the biosynthetic pathway of the toxin.

scholarly journals Characterization of the Saframycin A Gene Cluster from Streptomyces lavendulae NRRL 11002 Revealing a Nonribosomal Peptide Synthetase System for Assembling the Unusual Tetrapeptidyl Skeleton in an Iterative Manner

2007 ◽  
Vol 190 (1) ◽  
pp. 251-263 ◽  
Author(s):  
Lei Li ◽  
Wei Deng ◽  
Jie Song ◽  
Wei Ding ◽  
Qun-Fei Zhao ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Nonribosomal Peptide Synthetase ◽  
Combinatorial Biosynthesis ◽  
Common Mechanism ◽  
Nonribosomal Peptide ◽  
Streptomyces Lavendulae ◽  
Peptide Synthetase

ABSTRACT Saframycin A (SFM-A), produced by Streptomyces lavendulae NRRL 11002, belongs to the tetrahydroisoquinoline family of antibiotics, and its core is structurally similar to the core of ecteinascidin 743, which is a highly potent antitumor drug isolated from a marine tunicate. In this study, the biosynthetic gene cluster for SFM-A was cloned and localized to a 62-kb contiguous DNA region. Sequence analysis revealed 30 genes that constitute the SFM-A gene cluster, encoding an unusual nonribosomal peptide synthetase (NRPS) system and tailoring enzymes and regulatory and resistance proteins. The results of substrate prediction and in vitro characterization of the adenylation specificities of this NRPS system support the hypothesis that the last module acts in an iterative manner to form a tetrapeptidyl intermediate and that the colinearity rule does not apply. Although this mechanism is different from those proposed for the SFM-A analogs SFM-Mx1 and safracin B (SAC-B), based on the high similarity of these systems, it is likely they share a common mechanism of biosynthesis as we describe here. Construction of the biosynthetic pathway of SFM-Y3, an aminated SFM-A, was achieved in the SAC-B producer (Pseudomonas fluorescens). These findings not only shed new insight on tetrahydroisoquinoline biosynthesis but also demonstrate the feasibility of engineering microorganisms to generate structurally more complex and biologically more active analogs by combinatorial biosynthesis.

scholarly journals Characterization of AusA: A Dimodular Nonribosomal Peptide Synthetase Responsible for the Production of Aureusimine Pyrazinones

Biochemistry ◽  
2013 ◽  
Vol 52 (5) ◽  
pp. 926-937 ◽  
Author(s):  
Daniel J. Wilson ◽  
Ce Shi ◽  
Aaron M. Teitelbaum ◽  
Andrew M. Gulick ◽  
Courtney C. Aldrich
Keyword(s):  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase

scholarly journals In Vitro Characterization of a Heterologously Expressed Nonribosomal Peptide Synthetase Involved in Phosphinothricin Tripeptide Biosynthesis

Biochemistry ◽  
2009 ◽  
Vol 48 (23) ◽  
pp. 5054-5056 ◽  
Author(s):  
Jin-Hee Lee ◽  
Bradley S. Evans ◽  
Gongyong Li ◽  
Neil L. Kelleher ◽  
Wilfred A. van der Donk
Keyword(s):  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
In Vitro Characterization ◽  
Peptide Synthetase
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