Genome-guided discovery of diverse natural products from Burkholderia sp

Abstract

Burkholderia species have emerged as a new source of diverse natural products. This mini-review covers all of the natural products discovered in recent years from Burkholderia sp. by genome-guided approaches--these refer to the use of bacterial genome sequence as an entry point for in silico structural prediction, wet lab experimental design, and execution. While reliable structural prediction based on cryptic biosynthetic gene cluster sequence was not always possible due to noncanonical domains and/or module organization of a deduced biosynthetic pathway, a molecular genetic method was often employed to detect or alter the expression level of the gene cluster to achieve an observable phenotype, which facilitated downstream natural product purification and identification. Those examples of natural product discovery from Burkholderia sp. provide practical guidance for future exploration of Gram-negative bacteria as a new source of natural products.

Fig. 1

Structures of betulinans A–C, terferol, BTH-II0204-207:A–D (1–4) and BPSS2111-2113:A–C (5–7). Only natural products discovered from Burkholderia sp. through genome-guided approaches are given a bold numerical number in parenthesis while reference compounds are not. This rule applies to all figures in this mini-review.

Fig. 2

Structures of microcin J25 and capistruin (8) drawn with 1-letter amino acid abbreviations and residue numbers due to their large sizes and a lasso confirmation.

Fig. 3

Structures of an N-acyl homoserine lactone of Pseudomonas aeroginosa, malleilactone (9) and its tantomer burkholderic acid (10).

Fig. 4

Structures of thailandamide A (11), thailandamide B (12) and thailandamide lactone (13).

Fig. 5

Structures of FK228, thailandepsin A (burkholdac B; 14), thailandepsin B (15), thailandepsin C (burkholdac A; 16), thailandepsin D (17), thailandepsin E (18), and thailandepsin F (19).

Fig. 6

Structures of FR901464, thailanstatin A (20), thailanstatin B (21), and thailanstatin C (22).

Fig. 7

Schematic depiction of the B. thailandnsis E264 genome consisting of chromosomes I and II. Twenty one predicted natural product biosynthetic gene clusters with the antiSMASH program [5,33] are marked with either a numerical number (uncharacterized) or a gene cluster designation followed by compound name(s).