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1. WO2017020043 - BIOSYNTHESIS OF POLYKETIDES

Publication Number WO/2017/020043
Publication Date 02.02.2017
International Application No. PCT/US2016/045037
International Filing Date 01.08.2016
IPC
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
1
Micro-organisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving micro-organisms or compositions thereof; Processes of preparing or isolating a composition containing a micro-organism; Culture media therefor
20
Bacteria; Culture media therefor
21
modified by introduction of foreign genetic material
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9
Enzymes, e.g. ligases (6.); Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating, or purifying enzymes
10
Transferases (2.)
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15
Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09
Recombinant DNA-technology
63
Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
79
Vectors or expression systems specially adapted for eukaryotic hosts
82
for plant cells
C12N 1/21 (2006.01)
C12N 9/10 (2006.01)
C12N 15/82 (2006.01)
CPC
C12N 9/1029
C12P 17/06
C12P 7/26
C12P 7/42
C12Y 203/01009
Applicants
  • WILLIAM MARSH RICE UNIVERSITY [US/US]; 6100 Main Street Houston, TX 77005, US
Inventors
  • GONZALEZ, Ramon; US
  • CHEONG, Seokjung; US
  • CLOMBURG, James, M.; US
Agents
  • VALOIR, Tamsen; US
Priority Data
62/198,76430.07.2015US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) BIOSYNTHESIS OF POLYKETIDES
(FR) BIOSYNTHÈSE DE POLYCÉTIDES
Abstract
(EN)
This disclosure generally relates to the use of microorganisms to make various functionalized polyketides through polyketoacyl-CoA thiolase-catalyzed non-decarboxylative condensation reactions instead of decarboxylative reactions catalyzed by polyketide synthases. Native or engineered polyketoacyl-CoA thiolases catalyze the non-decarboxylative Claisen condensation in an iterative manner (i.e. multiple rounds) between two either unsubstituted or functionalized ketoacyl-CoAs (and polyketoacyl-CoAs) serving as the primers and acyl- CoAs serving as the extender unit to generate (and elongate) polyketoacyl-CoAs. Before the next round of polyketoacyl-CoA thiolase reaction, the β-keto group of the polyketide chain of polyketoacyl-CoA can be reduced and modified step-wise by 3-OH-polyketoacyl-CoA dehydrogenase or polyketoenoyl-CoA hydratase or polyketoenoyl-CoA reductase. Dehydrogenase converts the β-keto group to β-hydroxy group. Hydratase converts the β- hydroxy group to α-β-double-bond. Reductase converts the α-β-double-bond to single bond. Spontaneous or thioesterase catalyzed termination reaction terminates the elongation of polyketide chain of polyketoacyl-CoA at any point through CoA removal and spontaneous reactions rearrange the structure, generating the final functional polyketide products.
(FR)
La présente invention concerne d'une façon générale l'utilisation de microorganismes pour produire divers polycétides fonctionnalisés par des réactions de condensation non décarboxylantes catalysées par la polycétoacyl-CoA thiolase au lieu de réactions décarboxylantes catalysées par des polycétide synthases. Des polycétoacyl-CoA thiolases natives ou modifiées catalysent la condensation de Claisen non décarboxylante de manière itérative (c'est-à-dire en multiples cycles) entre deux cétoacyl-CoA (et polycétoacyl-CoA) soit non substitués soit fonctionnalisés servant d'amorces et des acyl-CoA servant d'unité d'extension pour produire (et allonger) des polycétoacyl-CoA. Avant le cycle suivant de réaction avec la polycétoacyl-CoA thiolase, le groupe ß-céto de la chaîne polycétide du polycétoacyl-CoA peut être réduit et modifié par étapes par la 3-OH-polycétoacyl-CoA déshydrogénase ou la polycétoénoyl-CoA hydratase ou la polycétoénoyl-CoA réductase. La déshydrogénase convertit le groupe ß-céto en groupe ß-hydroxy. L'hydratase convertit le groupe ß-hydroxy en double liaison α-β. La réductase convertit la double liaison α-β en simple liaison. Une réaction de terminaison spontanée ou catalysée par une thioestérase termine l'allongement de la chaîne polycétidique du polycétoacyl-CoA en un point quelconque par retrait du CoA et des réactions spontanées réarrangent la structure, en produisant des produits polycétidiques fonctionnels finaux.
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