The Long, Long Way to Bottromycin

Abstract

Although discovered already in the middle of last century, the bottromycins are a unique class of natural products, and a real challenge for all kind of researchers trying to get familiar with them. The structure elucidation was a tour de force and last over 50 years. Synthetic approaches were also painful and it was actually the first and so far only synthesis which confirmed/revised the previously proposed structures. Recent investigations on the biosynthetic pathway indicate that the bottromycins belong to the ribosomally synthesized and posttranslational modified peptides, but that also the biosynthesis does not proceed along the "usual way". This review will cover the development of bottromycin research from the beginning until today, with a focus on synthetic studies, total synthesis and modifications.

Microparticles enhance the formation of seven major classes of natural products in native and metabolically engineered actinobacteria through accelerated morphological development

“…As shown, talc microparticles significantly increased the production of the macrocyclic peptides bottromycin A2 and Met‐bottromycin A2 in recombinant S. lividans TK24 DG2‐Km‐P41hyg + (Figure 2). Generally, bottromycins are difficult to obtain and their research has developed into a “nightmare” over the past 65 years (Kazmaier, 2020). Various homologous as well as heterologous producers provide bottromycins only in the low milligram range and even below 1 mg L −1 (Crone et al, 2016; Horbal et al, 2018; Huo et al, 2012).…”

“…Generally, bottromycins are difficult to obtain and their research has developed into a "nightmare" over the past 65 years (Kazmaier, 2020). Various homologous as well as heterologous producers provide bottromycins only in the low milligram range and even below 1 mg L −1 (Crone et al, 2016;Horbal et al, 2018;Huo et al, 2012).…”

“…The cyclopeptide was first isolated from cultures of Streptomyces bottropensis (Waisvisz et al, 1957) and is active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci (Kobayashi et al, 2010). Its complex biosynthesis involves a unique posttranslational macrocyclization step (Huo et al, 2012) and has posed enormous challenges on bottromycin research and development over the past decades (Kazmaier, 2020).…”