Habitat-specific type I polyketide synthases in soils and street sediments

Abstract

Actinomycetes produce many pharmaceutically useful compounds through type I polyketide biosynthetic pathways. Soil has traditionally been an important source for these actinomycete-derived pharmaceuticals. As the rate of antibiotic discovery has decreased and the incidence of antibiotic resistance has increased, researchers have looked for alternatives to soil for bioprospecting. Street sediment, where actinomycetes make up a larger fraction of the bacterial population than in soil, is one such alternative environment. To determine if these differences in actinomycetal community structure are reflected in type I polyketide synthases (PKSI) distribution, environmental DNA from soils and street sediments was characterized by sequencing amplicons of PKSI-specific PCR primers. Amplicons covered two domains: the last 80 amino acids of the ketosynthase (KS) domain and the first 240 amino acids of the acyltransferase (AT) domain. One hundred and ninety clones from ten contrasting soils from six regions and nine street sediments from six cities were sequenced. Twenty-five clones from two earthworm-affected samples were also sequenced. UniFrac lineage-specific analysis identified two clades that clustered with actinomycetal GenBank matches that were street sediment-specific, one similar to the PKSI segment of the mycobactin siderophore involved in mycobacterial virulence. A clade of soil-specific sequences clustered with GenBank matches from the ambruticin and jerangolid pathways of Sorangium cellulosum. All three of these clades were found in sites >700 km apart. Street sediments are enriched in actinomycetal PKSIs. Non-actinomycetal PKSI pathways may be more chemically diverse than actinomycetal PKSIs. Common soil and street sediment PKIs are globally distributed.

An Evolutionary Model Encompassing Substrate Specificity and Reactivity of Type I Polyketide Synthase Thioesterases

“…Phylogenic analysis of type I PKS catalytic domains has shown that substrate specificity or reactivity of the domains often has a primary sequence determinant. For example, the acyltransferase (AT) domains cluster into malonyl‐CoA‐ and methylmalonyl‐CoA‐specific clades 3–6. β‐ketosynthase (KS) domains from trans AT pathways cluster based on the substitution at the α and β carbons of the upstream polyketide intermediates 7.…”

Dark, rare and inspirational microbial matter in the extremobiosphere: 16 000 m of bioprospecting campaigns

“…While recognizing that more mundane environments can contain novelty for the bioprospector (e.g. forest soil [73], street sediments [74]) we opine that the case for prioritizing extreme biomes is sound as it moves bioprospecting action away from well-probed terrestrial streptomycetes towards microbial communities that have evolved under harsh selective conditions during the course of which novel biochemistry has been generated [75]. As Rateb et al report [66], a total of 46 natural products representing diverse chemical classes have been isolated from Atacama Desert actinobacteria during the past 7 years.…”

Sampling Terrestrial Environments for Bacterial Polyketides

“…This database was disproportionately actinomycetal possibly biasing the analysis. However this result was confirmed when the sequences were reanalyzed with a broader range of non-actinomycetal PKS domains [ 104 ].…”

“…In our work we compared PKSI amplicons of KS and AT from street sediments [ 104 ], which are enriched with Actinomycetes, and soils [ 46 ]. Many soil amplicons clustered with myxobacterial sequences.…”