Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan.
J Ind Microbiol Biotechnol. 2019 Mar;46(3-4):363-374. doi: 10.1007/s10295-018-2100-y. Epub 2018 Nov 28.
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.
细菌次生代谢产物（SM）是药物先导的丰富来源，特别是许多代谢产物已从放线菌中分离出来。最近的基因组序列项目表明，放线菌中蕴藏的次生代谢产物生物合成基因簇（SM-BGCs）比以前预期的要多得多。然而，在标准培养条件下，放线菌中的大部分 SM-BGC 处于休眠和隐匿状态。因此，需要一种广泛适用的隐匿性 SM-BGC 激活方法来获得新型 SM。最近，人们发现与含有分枝菌酸的细菌（MACB）共培养可广泛激活放线菌中的隐匿性 SM-BGC。这种“组合培养”方法（使用 MACB 作为放线菌伙伴的共培养方法）易于应用于广泛的放线菌，实际上，迄今为止已经从 12 株放线菌中成功获得了 33 种新型 SM。本文综述了组合培养方法的发展、应用和机制分析。
