Abstract
Filamentous actinomycetes are commercially widely used as producers of natural products (in particular antibiotics) and of industrial enzymes. However, the mycelial lifestyle of actinomycetes, resulting in highly viscous broths and unfavorable pellet formation, has been a major bottleneck in their commercialization. Here we describe the successful morphological engineering of industrially important streptomycetes through controlled expression of the morphogene ssgA. This led to improved growth of many industrial and reference streptomycetes, with fragmentation of the mycelial clumps resulting in significantly enhanced growth rates in batch fermentations of Streptomyces coelicolor and Streptomyces lividans. Product formation was also stimulated, with a twofold increase in yield of enzyme production by S. lividans. We anticipate that the use of the presented methodology will make actinomycetes significantly more attractive as industrial and sustainable production hosts.
MeSH Terms
Bacterial Proteins/genetics
Culture Media
Fermentation
Gene Expression Regulation, Bacterial
Genetic Engineering/methods
Industrial Microbiology/methods
Streptomyces/classification,genetics,growth & development,metabolism
Chemicals
Bacterial Proteins
Culture Media
ssgA protein, bacterial
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
van Wezel Gilles P
Microbial Development, LIC, Leiden University, 2300RA Leiden, The Netherlands. g.wezel@chem.leidenuniv.nl
Krabben Preben
Traag Bjørn A
Keijser Bart J F
Kerste Rob
Vijgenboom Erik
Heijnen Josef J
Kraal Barend
References (24)
24 references, click to expand
-
ssgA is essential for sporulation of Streptomyces coelicolor A3(2) and affects hyphal development by stimulating septum formation.
J Bacteriol. 2000 Oct;182(20):5653-62
PMID: 11004161
-
A quantitative approach to characterizing cell lysis caused by mechanical agitation of Streptomyces clavuligerus.
Biotechnol Prog. 2001 Mar-Apr;17(2):336-47
PMID: 11312712
-
Effects of increased and deregulated expression of cell division genes on the morphology and on antibiotic production of streptomycetes.
Antonie Van Leeuwenhoek. 2000 Dec;78(3-4):269-76
PMID: 11386349
-
Decreasing the hyphal branching rate of Saccharopolyspora erythraea NRRL 2338 leads to increased resistance to breakage and increased antibiotic production.
Biotechnol Bioeng. 2002 Apr 20;78(2):141-6
PMID: 11870604
-
Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).
Nature. 2002 May 9;417(6885):141-7
PMID: 12000953
-
A genomics-guided approach for discovering and expressing cryptic metabolic pathways.
Nat Biotechnol. 2003 Feb;21(2):187-90
PMID: 12536216
-
Transcriptional switch on of ssgA by A-factor, which is essential for spore septum formation in Streptomyces griseus.
J Bacteriol. 2003 Feb;185(4):1273-83
PMID: 12562798
-
The Streptomyces genome--be prepared!
Nat Biotechnol. 2003 May;21(5):505-6
PMID: 12721573
-
A 'Fine' chemical industry for life science products: green solutions to chemical challenges.
Adv Biochem Eng Biotechnol. 2003;80:69-113
PMID: 12747542
-
Oxidative stress in submerged cultures of fungi.
Crit Rev Biotechnol. 2003;23(4):267-302
PMID: 15224892
-
Transcription of the sporulation gene ssgA is activated by the IclR-type regulator SsgR in a whi-independent manner in Streptomyces coelicolor A3(2).
Mol Microbiol. 2004 Aug;53(3):985-1000
PMID: 15255907
-
Quantifying the accessibility of the metagenome by random expression cloning techniques.
Environ Microbiol. 2004 Sep;6(9):879-86
PMID: 15305913
-
Purification and characterization of a tyrosinase from Streptomyces glaucescens.
Eur J Biochem. 1972 Dec 18;31(3):427-37
PMID: 4631007
-
Cloning and expression of the tyrosinase gene from Streptomyces antibioticus in Streptomyces lividans.
J Gen Microbiol. 1983 Sep;129(9):2703-14
PMID: 6313861
-
Production of beta-lactam antibiotics and its regulation.
Proc Natl Sci Counc Repub China B. 1991 Oct;15(4):251-65
PMID: 1815263
-
Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp.
Gene. 1992 Jul 1;116(1):43-9
PMID: 1628843
-
Pellet formation and fragmentation in submerged cultures of Penicillium chrysogenum and its relation to penicillin production.
Biotechnol Prog. 1995 Jan-Feb;11(1):93-8
PMID: 7765991
-
Genetics of antibiotic production in Streptomyces coelicolor A3(2), a model streptomycete.
Biotechnology. 1995;28:65-102
PMID: 8688641
-
1995 Colworth Prize Lecture. The regulation of antibiotic production in Streptomyces coelicolor A3(2).
Microbiology. 1996 Jun;142 ( Pt 6):1335-44
PMID: 8704973
-
Expression analysis of the ssgA gene product, associated with sporulation and cell division in Streptomyces griseus.
Microbiology. 1997 Apr;143 ( Pt 4):1077-86
PMID: 9141673
-
Fed-batch bioproduction of spectinomycin.
Adv Biochem Eng Biotechnol. 1998;59:1-46
PMID: 9435459
-
Mycotechnology: the role of fungi in biotechnology.
J Biotechnol. 1998 Dec 11;66(2-3):101-7
PMID: 9866863
-
Expression of the melC operon in several Streptomyces strains is positively regulated by AdpA, an AraC family transcriptional regulator involved in morphological development in Streptomyces coelicolor.
J Bacteriol. 2005 May;187(9):3180-7
PMID: 15838045
-
SsgA-like proteins determine the fate of peptidoglycan during sporulation of Streptomyces coelicolor.
Mol Microbiol. 2005 Nov;58(4):929-44
PMID: 16262781