The Clavulanic Acid Strain Improvement Program at DSM Anti‐Infectives

Koekman, Bert; Hans, Marcus

doi:10.1002/9781118433034.ch6

Cited by 1 publication

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the improvement program the growth characteristics were also improved upon, which contributed both to the production titres and the fermentability of the strain [ 13 ]. Production of clavulanic acid by Streptomyces clavuligerus underwent a similar improvement program [ 14 ]. Classical strain improvement, however, is also slow and labour-intensive, and typically associated with a large number of mutations that may later slow down further improvement.…”

Section: Introductionmentioning

confidence: 99%

A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories

et al. 2015

View full text Add to dashboard Cite

BackgroundStreptomycetes produce a plethora of natural products including antibiotics and anticancer drugs, as well as many industrial enzymes. Their mycelial life style is a major bottleneck for industrial exploitation and over decades strain improvement programs have selected production strains with better growth properties. Uncovering the nature of the underlying mutations should allow the ready transfer of desirable traits to other production hosts.ResultsHere we report that the mat gene cluster, which was identified through reverse engineering of a non-pelleting mutant selected in a chemostat, is key to pellet formation of Streptomyces lividans. Deletion of matA or matB, which encode putative polysaccharide synthases, effects mycelial metamorphosis, with very small and open mycelia. Growth rate and productivity of the matAB null mutant were increased by over 60% as compared to the wild-type strain.ConclusionHere, we present a way to counteract pellet formation by streptomycetes, which is one of the major bottlenecks in their industrial application. The mat locus is an ideal target for rational strain design approaches aimed at improving streptomycetes as industrial production hosts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-015-0224-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%