Macrolide biosynthesis. 7. Incorporation of polyketide chain elongation intermediates into methymycin

1993 ◽  
Vol 115 (2) ◽  
pp. 522-526 ◽  
Author(s):  
David E. Cane ◽  
Ralph H. Lambalot ◽  
P. C. Prabhakaran ◽  
Walter R. Ott
Keyword(s):  
Chain Elongation ◽  
Polyketide Chain

Macrolide biosynthesis. 6 Mechanism of polyketide chain elongation

1991 ◽  
Vol 32 (40) ◽  
pp. 5457-5460 ◽  
Author(s):  
David E. Cane ◽  
P.C. Prabhakaran ◽  
Weitian Tan ◽  
Walter R. Ott
Keyword(s):  
Chain Elongation ◽  
Polyketide Chain

ChemInform Abstract: Macrolide Biosynthesis. Part 7. Incorporation of Polyketide Chain Elongation Intermediates into Methymycin.

ChemInform ◽  
2010 ◽  
Vol 24 (21) ◽  
pp. no-no
Author(s):  
D. E. CANE ◽  
R. H. LAMBALOT ◽  
P. C. PRABHAKARAN ◽  
W. R. OTT
Keyword(s):  
Chain Elongation ◽  
Polyketide Chain

scholarly journals Thioesterases and the Premature Termination of Polyketide Chain Elongation in Rifamycin B Biosynthesis by Amycolatopsis mediterranei S699.

2000 ◽  
Vol 53 (5) ◽  
pp. 484-495 ◽  
Author(s):  
YUKIKO DOI-KATAYAMA ◽  
YEO JOON YOON ◽  
CHA-YONG CHOI ◽  
TIN-WEIN YU ◽  
HEINZ G. FLOSS ◽  
...  
Keyword(s):  
Premature Termination ◽  
Chain Elongation ◽  
Amycolatopsis Mediterranei ◽  
Polyketide Chain ◽  
Rifamycin B

scholarly journals Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

2016 ◽  
Vol 12 ◽  
pp. 2164-2172 ◽  
Author(s):  
Hui Hong ◽  
Yuhui Sun ◽  
Yongjun Zhou ◽  
Emily Stephens ◽  
Markiyan Samborskyy ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Strong Support ◽  
Artificial Chromosome ◽  
Chain Extension ◽  
Chain Elongation ◽  
Starter Unit ◽  
Polyketide Chain ◽  
Streptomyces Olivaceus ◽  
Streptomyces Malaysiensis

The assembly-line synthases that produce bacterial polyketide natural products follow a modular paradigm in which each round of chain extension is catalysed by a different set or module of enzymes. Examples of deviation from this paradigm, in which a module catalyses either multiple extensions or none are of interest from both a mechanistic and an evolutionary viewpoint. We present evidence that in the biosynthesis of the 36-membered macrocyclic aminopolyol lactones (marginolactones) azalomycin and kanchanamycin, isolated respectively from Streptomyces malaysiensis DSM4137 and Streptomyces olivaceus Tü4018, the first extension module catalyses both the first and second cycles of polyketide chain extension. To confirm the integrity of the azl gene cluster, it was cloned intact on a bacterial artificial chromosome and transplanted into the heterologous host strain Streptomyces lividans, which does not possess the genes for marginolactone production. When furnished with 4-guanidinobutyramide, a specific precursor of the azalomycin starter unit, the recombinant S. lividans produced azalomycin, showing that the polyketide synthase genes in the sequenced cluster are sufficient to accomplish formation of the full-length polyketide chain. This provides strong support for module iteration in the azalomycin and kanchanamycin biosynthetic pathways. In contrast, re-sequencing of the gene cluster for biosynthesis of the polyketide β-lactone ebelactone in Streptomyces aburaviensis has shown that, contrary to a recently-published proposal, the ebelactone polyketide synthase faithfully follows the colinear modular paradigm.

scholarly journals Mechanism and Stereochemistry of Polyketide Chain Elongation and Methyl Group Epimerization in Polyether Biosynthesis

2017 ◽  
Vol 139 (8) ◽  
pp. 3283-3292 ◽  
Author(s):  
Xinqiang Xie ◽  
Ashish Garg ◽  
Chaitan Khosla ◽  
David E. Cane
Keyword(s):  
Chain Elongation ◽  
Methyl Group ◽  
Polyketide Chain

scholarly journals Reconstitution of the FK228 Biosynthetic Pathway Reveals Cross Talk between Modular Polyketide Synthases and Fatty Acid Synthase

2010 ◽  
Vol 77 (4) ◽  
pp. 1501-1507 ◽  
Author(s):  
Shane R. Wesener ◽  
Vishwakanth Y. Potharla ◽  
Yi-Qiang Cheng
Keyword(s):  
Fatty Acid ◽  
Cross Talk ◽  
Biosynthetic Pathway ◽  
Fatty Acid Synthase ◽  
Polyketide Synthase ◽  
Fatty Acid Biosynthesis ◽  
Chain Elongation ◽  
E Coli ◽  
Genetic Components ◽  
Polyketide Chain

ABSTRACTFunctional cross talk between fatty acid biosynthesis and secondary metabolism has been discovered in several cases in microorganisms; none of them, however, involves a modular biosynthetic enzyme. Previously, we reported a hybrid modular nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) pathway for the biosynthesis of FK228 anticancer depsipeptide inChromobacterium violaceumstrain 968. This pathway contains two PKS modules on the DepBC enzymes that lack a functional acyltransferase (AT) domain, and no apparent AT-encoding gene exists within the gene cluster or its vicinity. We report here that, through reconstitution of the FK228 biosynthetic pathway inEscherichia colicells, two essential genes,fabD1andfabD2, both encoding a putative malonyl coenzyme A (CoA) acyltransferase component of the fatty acid synthase complex, are positively identified to be involved in FK228 biosynthesis. Either gene product appears sufficient to complement the AT-less PKS modules on DepBC for polyketide chain elongation. Concurrently, a gene (sfp) encoding a putative Sfp-type phosphopantetheinyltransferase was identified to be necessary for FK228 biosynthesis as well. Most interestingly, engineeredE. colistrains carrying variable genetic components produced significant levels of FK228 under both aerobic and anaerobic cultivation conditions. Discovery of thetranscomplementation of modular PKSs by housekeeping ATs reveals natural product biosynthesis diversity. Moreover, demonstration of anaerobic production of FK228 by an engineered facultative bacterial strain validates our effort toward the engineering of novel tumor-targeting bioagents.

scholarly journals Engineering of chimeric polyketide synthases using SYNZIP docking domains

2018 ◽  
Author(s):  
Maja Klaus ◽  
Alicia D. D’Souza ◽  
Aleksandra Nivina ◽  
Chaitan Khosla ◽  
Martin Grininger
Keyword(s):  
Turnover Rate ◽  
Assembly Line ◽  
Polyketide Synthases ◽  
Chain Elongation ◽  
Different Types ◽  
Domain Interactions ◽  
Covalent Docking ◽  
Polyketide Chain ◽  
Extender Unit ◽  
Catalytic Cycles

AbstractEngineering of assembly line polyketide synthases (PKSs) to produce novel bioactive compounds has been a goal for over twenty years. The apparent modularity of PKSs has inspired many engineering attempts in which entire modules or single domains were exchanged. In recent years, it has become evident that certain domain-domain interactions are evolutionarily optimized, and if disrupted, cause a decrease of the overall turnover rate of the chimeric PKS. In this study, we compared different types of chimeric PKSs in order to define the least invasive interface and to expand the toolbox for PKS engineering. We generated bimodular chimeric PKSs in which entire modules were exchanged, while either retaining a covalent linker between heterologous modules or introducing a non-covalent docking domain- or SYNZIP domain-mediated interface. These chimeric systems exhibited non-native domain-domain interactions during intermodular polyketide chain translocation. They were compared to otherwise equivalent bimodular PKSs in which a non-covalent interface was introduced between the condensing and processing parts of a module, resulting in non-native domain interactions during the extender unit acylation and polyketide chain elongation steps of their catalytic cycles. We show that the natural PKS docking domains can be efficiently substituted with SYNZIP domains and that the newly introduced non-covalent interface between the condensing and processing parts of a module can be harnessed for PKS engineering. Additionally, we established SYNZIP domains as a new tool for engineering PKSs by efficiently bridging non-native interfaces without perturbing PKS activity.

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