Faculty Opinions recommendation of Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases.

Aromatic polyketides make up a large class of natural products with diverse bioactivity. During biosynthesis, linear poly-β-ketone intermediates are regiospecifically cyclized, yielding molecules with defined cyclization patterns that are crucial for polyketide bioactivity. The aromatase/cyclases (ARO/CYCs) are responsible for regiospecific cyclization of bacterial polyketides. The two most common cyclization patterns are C7–C12 and C9–C14 cyclizations. We have previously characterized three monodomain ARO/CYCs: ZhuI, TcmN, and WhiE. The last remaining uncharacterized class of ARO/CYCs is the di-domain ARO/CYCs, which catalyze C7–C12 cyclization and/or aromatization. Di-domain ARO/CYCs can further be separated into two subclasses: “nonreducing” ARO/CYCs, which act on nonreduced poly-β-ketones, and “reducing” ARO/CYCs, which act on cyclized C9 reduced poly-β-ketones. For years, the functional role of each domain in cyclization and aromatization for di-domain ARO/CYCs has remained a mystery. Here we present what is to our knowledge the first structural and functional analysis, along with an in-depth comparison, of the nonreducing (StfQ) and reducing (BexL) di-domain ARO/CYCs. This work completes the structural and functional characterization of mono- and di-domain ARO/CYCs in bacterial type II polyketide synthases and lays the groundwork for engineered biosynthesis of new bioactive polyketides.

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Functional analysis of environmental DNA-derived type II polyketide synthases reveals structurally diverse secondary metabolites

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1103921108 ◽

2011 ◽

Vol 108 (31) ◽

pp. 12629-12634 ◽

Cited By ~ 83

Author(s):

Z. Feng ◽

D. Kallifidas ◽

S. F. Brady

Keyword(s):

Functional Analysis ◽

Secondary Metabolites ◽

Environmental Dna ◽

Polyketide Synthases ◽

Type Ii

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KORÁNYI’S LEMMA FOR HOMOGENEOUS SIEGEL DOMAINS OF TYPE II. APPLICATIONS AND EXTENDED RESULTS

Bulletin of the Australian Mathematical Society ◽

10.1017/s0004972714000033 ◽

2014 ◽

Vol 90 (1) ◽

pp. 77-89 ◽

Cited By ~ 2

Author(s):

DAVID BÉKOLLÉ ◽

HIDEYUKI ISHI ◽

CYRILLE NANA

Keyword(s):

Functional Analysis ◽

Bergman Kernel ◽

Atomic Decomposition ◽

Bergman Spaces ◽

Decomposition Theorem ◽

Interpolation Theorem ◽

Type Ii ◽

Siegel Domain ◽

Homogeneous Case ◽

Siegel Domains

AbstractWe show that the modulus of the Bergman kernel $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}B(z, \zeta )$ of a general homogeneous Siegel domain of type II is ‘almost constant’ uniformly with respect to $z$ when $\zeta $ varies inside a Bergman ball. The control is expressed in terms of the Bergman distance. This result was proved by A. Korányi for symmetric Siegel domains of type II. Subsequently, R. R. Coifman and R. Rochberg used it to establish an atomic decomposition theorem and an interpolation theorem by functions in Bergman spaces $A^p$ on these domains. The atomic decomposition theorem and the interpolation theorem are extended here to the general homogeneous case using the same tools. We further extend the range of exponents $p$ via functional analysis using recent estimates.

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Genetic construction and functional analysis of hybrid polyketide synthases containing heterologous acyl carrier proteins.

Journal of Bacteriology ◽

10.1128/jb.175.8.2197-2204.1993 ◽

1993 ◽

Vol 175 (8) ◽

pp. 2197-2204 ◽

Cited By ~ 57

Author(s):

C Khosla ◽

R McDaniel ◽

S Ebert-Khosla ◽

R Torres ◽

D H Sherman ◽

...

Keyword(s):

Functional Analysis ◽

Polyketide Synthases ◽

Carrier Proteins ◽

Acyl Carrier Proteins

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Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase

Applied and Environmental Microbiology ◽

10.1128/aem.72.4.2573-2580.2006 ◽

2006 ◽

Vol 72 (4) ◽

pp. 2573-2580 ◽

Cited By ~ 83

Author(s):

Wenjun Zhang ◽

Brian D. Ames ◽

Shiou-Chuan Tsai ◽

Yi Tang

Keyword(s):

Polyketide Synthase ◽

Major Product ◽

Polyketide Synthases ◽

Type Ii ◽

Streptomyces Rimosus ◽

Aromatic Polyketides ◽

Starter Unit ◽

Necessary And Sufficient ◽

Bacterial Type

ABSTRACT Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs is an important step toward the rational and combinatorial manipulation of tetracycline biosynthesis. To this end, we have sequenced the gene cluster of oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence analysis revealed a total of 21 genes between the otrA and otrB resistance genes. We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate starter unit that is a universal building block for tetracycline compounds. In vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are necessary and sufficient for the biosynthesis of amidated polyketides. A novel alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy-encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide backbone and cyclized with novel regioselectivity. The expression of OxyD with a heterologous minimal PKS did not afford similarly amidated polyketides, suggesting that the oxy-encoded minimal PKS possesses novel starter unit specificity.

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Functional analysis of the type II toxin–antitoxin systems of the MazEF and RelBE families in Bifidobacterium longum subsp. infantis ATCC 15697

Anaerobe ◽

10.1016/j.anaerobe.2015.07.007 ◽

2015 ◽

Vol 35 ◽

pp. 59-67 ◽

Cited By ~ 8

Author(s):

Olga Averina ◽

Maria Alekseeva ◽

Andrei Shkoporov ◽

Valery Danilenko

Keyword(s):

Functional Analysis ◽

Bifidobacterium Longum ◽

Type Ii

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Effect of the DaunorubicindpsHGene on the Choice of Starter Unit and Cyclization Pattern Reveals That Type II Polyketide Synthases Can Be Unfaithful yet Intriguing

Journal of the American Chemical Society ◽

10.1021/ja970946h ◽

1997 ◽

Vol 119 (31) ◽

pp. 7392-7393 ◽

Cited By ~ 18

Author(s):

Martin Gerlitz ◽

Guido Meurer ◽

Evelyn Wendt-Pienkowski ◽

Krishnamurthy Madduri ◽

C. Richard Hutchinson

Keyword(s):

Polyketide Synthases ◽

Type Ii ◽

Starter Unit

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Molecular Genetics and Biochemistry of Type II Polyketide Synthases from the Perspective of Tetracenomycin C Biosynthesis in Streptomyces glaucescens.

Actinomycetologica ◽

10.3209/saj.6_49 ◽

1992 ◽

Vol 6 (2) ◽

pp. 49-68 ◽

Cited By ~ 1

Author(s):

C. Richard Hutchinson ◽

Heinrich Decker ◽

Haideh Motamedi ◽

Ben Shen ◽

Richard G. Summers ◽

...

Keyword(s):

Molecular Genetics ◽

Polyketide Synthases ◽

Type Ii ◽

Streptomyces Glaucescens

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Biosynthesis of Polyketides in Streptomyces

Microorganisms ◽

10.3390/microorganisms7050124 ◽

2019 ◽

Vol 7 (5) ◽

pp. 124 ◽

Cited By ~ 12

Author(s):

Chandra Risdian ◽

Tjandrawati Mozef ◽

Joachim Wink

Keyword(s):

Secondary Metabolites ◽

Structure And Function ◽

Polyketide Synthases ◽

Type I ◽

Type Ii ◽

Filamentous Form ◽

Gram Positive Bacteria ◽

Wide Range ◽

Different Types ◽

And Function

Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol, and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks, and sponges. Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of the polyketides producers. Some examples of polyketides produced by Streptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin, and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in Streptomyces responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in Streptomyces with three structurally-different types of PKSs.

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