%0 Journal Article
%T Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds.
%A Kudo K
%A Nishimura T
%A Izumikawa M
%A Kozone I
%A Hashimoto J
%A Fujie M
%A Suenaga H
%A Ikeda H
%A Satoh N
%A Shin-Ya K
%J J Antibiot (Tokyo)
%V 77
%N 5
%D 2024 May 4
%M 38438499
%F 3.424
%R 10.1038/s41429-024-00711-9
%X The biosynthetic gene clusters (BGCs) for the macrocyclic lactone-based polyketide compounds are extremely large-sized because the polyketide synthases that generate the polyketide chains of the basic backbone are of very high molecular weight. In developing a heterologous expression system for the large BGCs amenable to the production of such natural products, we selected concanamycin as an appropriate target. We obtained a bacterial artificial chromosome (BAC) clone with a 211-kb insert harboring the entire BGC responsible for the biosynthesis of concanamycin. Heterologous expression of this clone in a host strain, Streptomyces avermitilis SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as ent-gephyromycin and a novel compound that was designated JBIR-157. We describe herein sequencing and expression studies performed on these BGCs, demonstrating the utility of large BAC clones for the heterologous expression of cryptic or near-silent loci.