Identification and engineering of 32 membered antifungal macrolactone notonesomycins.

Antifungal Agents / isolation & purification Cloning, Molecular Macrolides / isolation & purification Multigene Family Streptomyces / genetics
Biosynthetic gene cluster CRISPR–Cas9 Natural product Polyketide Streptomyces antibiotic regulatory protein Sulfation

Journal

Microbial cell factories
ISSN: 1475-2859
Titre abrégé: Microb Cell Fact
Pays: England
ID NLM: 101139812

Informations de publication

Date de publication:
19 Mar 2020
Historique:
received: 10 10 2019
accepted: 12 03 2020
entrez: 21 3 2020
pubmed: 21 3 2020
medline: 22 10 2020
Statut: epublish

Résumé

Notonesomycin A is a 32-membered bioactive glycosylated macrolactone known to be produced by Streptomyces aminophilus subsp. notonesogenes 647-AV1 and S. aminophilus DSM 40186. In a high throughput antifungal screening campaign, we identified an alternative notonesomycin A producing strain, Streptomyces sp. A793, and its biosynthetic gene cluster. From this strain, we further characterized a new more potent antifungal non-sulfated analogue, named notonesomycin B. Through CRISPR-Cas9 engineering of the biosynthetic gene cluster, we were able to increase the production yield of notonesomycin B by up to 18-fold as well as generate a strain that exclusively produces this analogue.

Identifiants

DOI: 10.1186/s12934-020-01328-x PMID: 32192516 PMC: PMC7081687
pubmed: 32192516
doi: 10.1186/s12934-020-01328-x
pii: 10.1186/s12934-020-01328-x
pmc: PMC7081687
doi:

Substances chimiques

Antifungal Agents 0
Macrolides 0
notonesomycin A 102525-63-3

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

71

Subventions

Organisme : National Research Foundation Singapore
ID : NRF2013-THE001-094

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Auteurs

Falicia Goh (F)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.
Biotransformation Innovation Platform, A*STAR, 61 Biopolis Drive, Proteos Level 4, Singapore, 138673, Singapore.

Mingzi M Zhang (MM)

Metabolic Engineering, Functional Molecules & Polymers, Institute of Chemical and Engineering Sciences, A*STAR, 31 Biopolis Way, Nanos #01-01, Singapore, 138669, Singapore.
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan, R.O.C.

Tian Ru Lim (TR)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Kia Ngee Low (KN)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Choy Eng Nge (CE)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Elena Heng (E)

Molecular Engineering Laboratory, Institute of Bioengineering and Nanotechnology, A*STAR, 31 Biopolis Way, Nanos, Singapore, 138669, Singapore.

Wan Lin Yeo (WL)

Metabolic Engineering, Functional Molecules & Polymers, Institute of Chemical and Engineering Sciences, A*STAR, 31 Biopolis Way, Nanos #01-01, Singapore, 138669, Singapore.

Fernanda L Sirota (FL)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Sharon Crasta (S)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Zann Tan (Z)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Veronica Ng (V)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Chung Yan Leong (CY)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Huibin Zhang (H)

Genome Institute of Singapore, A*STAR, 60 Biopolis Street, Genome #02-01, Singapore, 138672, Singapore.

Alexander Lezhava (A)

Genome Institute of Singapore, A*STAR, 60 Biopolis Street, Genome #02-01, Singapore, 138672, Singapore.

Swaine L Chen (SL)

Genome Institute of Singapore, A*STAR, 60 Biopolis Street, Genome #02-01, Singapore, 138672, Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 10, Singapore, 119228, Singapore.

Shawn S Hoon (SS)

Molecular Engineering Laboratory, Institute of Bioengineering and Nanotechnology, A*STAR, 31 Biopolis Way, Nanos, Singapore, 138669, Singapore.

Frank Eisenhaber (F)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.
School of Computer Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore, 637553, Singapore.

Birgit Eisenhaber (B)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Yoganathan Kanagasundaram (Y)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.

Fong T Wong (FT)

Molecular Engineering Laboratory, Institute of Bioengineering and Nanotechnology, A*STAR, 31 Biopolis Way, Nanos, Singapore, 138669, Singapore. wongft@ibn.a-star.edu.sg.

Siew Bee Ng (SB)

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore. ngsb@bii.a-star.edu.sg.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antifongiques › Identification and engineering of 32 membered...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Clonage moléculaire › Identification and engineering of 32 membered...
questionsmedicales.fr › Composés polycycliques › Composés macrocycliques › Polycétides › Macrolides › Identification and engineering of 32 membered...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Famille multigénique › Identification and engineering of 32 membered...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets sporulés à Gram positif › Streptomycetaceae › Streptomyces › Identification and engineering of 32 membered...