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Review
. 2019 Mar;46(3-4):363-374.
doi: 10.1007/s10295-018-2100-y. Epub 2018 Nov 28.

Activation of silent biosynthetic pathways and discovery of novel secondary metabolites in actinomycetes by co-culture with mycolic acid-containing bacteria

Shotaro Hoshino  1 , Hiroyasu Onaka  2   3 , Ikuro Abe  4   5
Affiliations
Review

Activation of silent biosynthetic pathways and discovery of novel secondary metabolites in actinomycetes by co-culture with mycolic acid-containing bacteria

Shotaro Hoshino et al. J Ind Microbiol Biotechnol. 2019 Mar.

Abstract

Bacterial secondary metabolites (SM) are rich sources of drug leads, and in particular, numerous metabolites have been isolated from actinomycetes. It was revealed by recent genome sequence projects that actinomycetes harbor much more secondary metabolite-biosynthetic gene clusters (SM-BGCs) than previously expected. Nevertheless, large parts of SM-BGCs in actinomycetes are dormant and cryptic under the standard culture conditions. Therefore, a widely applicable methodology for cryptic SM-BGC activation is required to obtain novel SM. Recently, it was discovered that co-culturing with mycolic-acid-containing bacteria (MACB) widely activated cryptic SM-BGCs in actinomycetes. This "combined-culture" methodology (co-culture methodology using MACB as the partner of actinomycetes) is easily applicable for a broad range of actinomycetes, and indeed, 33 novel SM have been successfully obtained from 12 actinomycetes so far. In this review, the development, application, and mechanistic analysis of the combined-culture method were summarized.

Keywords: Actinomycetes; Combined culture; Mycolic acid-containing bacteria (MACB); Secondary metabolite-biosynthetic gene clusters (SM-BGCs); Secondary metabolites (SM).

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