Phenolic Lipids Synthesized by Type III Polyketide Synthase Confer Penicillin Resistance on Streptomyces griseus

Abstract

Type III polyketide synthases (PKSs) found in plants, fungi, and bacteria synthesize a variety of aromatic polyketides. A Gram-positive, filamentous bacterium Streptomyces griseus contained an srs operon, in which srsA encoded a type III PKS, srsB encoded a methyltransferase, and srsC encoded a flavoprotein hydroxylase. Consistent with this annotation, overexpression of the srs genes in a heterologous host, Streptomyces lividans, showed that SrsA was a type III PKS of and was a the and was a the SrsA showed that SrsA of a of and of SrsA was in that the in a of and srsA which was and with the that the in the this that the with the of the and of the of a variety of found and of the Type III polyketide synthases (PKSs) found in plants, fungi, and bacteria synthesize a variety of aromatic polyketides. A Gram-positive, filamentous bacterium Streptomyces griseus contained an srs operon, in which srsA encoded a type III PKS, srsB encoded a methyltransferase, and srsC encoded a flavoprotein hydroxylase. Consistent with this annotation, overexpression of the srs genes in a heterologous host, Streptomyces lividans, showed that SrsA was a type III PKS of and was a the and was a the SrsA showed that SrsA of a of and of SrsA was in that the in a of and srsA which was and with the that the in the this that the with the of the and of the of a variety of found and of the Type III PKS, polyketide PKS, polyketide and that the of aromatic in and found that a type III PKS, in the Gram-positive, filamentous bacterium Streptomyces griseus the of a with and the the was the of a type III PKS of bacteria that type III in Streptomyces and of which type III in the of and which the in the the griseus and in and in and found a type III PKS, in type III PKS was SrsA of synthesize in a a of the was an srs of and srsC this the of the srs the in and in of the SrsA was of the of and of in Consistent with this overexpression of srsA in a heterologous host, Streptomyces lividans, the of with and in SrsA and and the of of the was srsA and srsB in lividans, of and srsC of showed that was a and was a the of the operon, a the and griseus in the was and of which that the and in the of the griseus in the of a of the with the that a of genes and in and that the a in the the that in and and and and A griseus was the of was Streptomyces of and srsC in a was with of was a Streptomyces of SrsA in an was and griseus in Streptomyces and with the an the of griseus the the of was of of srsA the of the in an was the of srsA with an and the the and a a the and the of srsB the was the and of in was the and of in of of srsA and srsB the was with and III with a the was the and of in was the and of in of of and srsC the srsC was the in srsC a the of srsB the the of srsC was with with a the and with a the was the and of in was the and of in was the and of in of the of the srsA a of the srsA was with with a the and with a the was the and of in was the and of in was the and of in of a the of srsA was in an and in the the and was with and with a and and the was the and of in was the of in of srsA with the in was with with a the the in the the the and with a the was the and of in was the and of in of was of of and of was the and the was A of the was with and with the was in of with and in a of was and of of and griseus the the that the was the with the was and the was was with and with was a of was with with with and the and the in a of and an was and in with a with and in a of of of a of and of and of a of and of of and of a of and of a of and of a of and of and of a of and of was and with the of and and and in the in and of was of and was the and the was a was and in and was was with and and with and SrsA was of was with a a of the SrsA was SrsA and the of of and in a of of and with of was and the in of of srsA in in the srsA was the with a of A the was with an the and with the the and a the was the and of in A the was with the the and a the and with a the was the and of in the was the and of in was in the of the in was with and griseus in the a of of the was a in which srsA was was a was that in of in the the and the of griseus and in of of was the with of and in of and was of was was the with of and of was the was was the and the was the of the with and with was and the was in of of the srs and of of the srs genes in of srsA the of and the of srsB with the of of the srs genes that an that was a of a a which of srsA a which of that the srs the srs was of in of that a type III PKS and SrsA showed in a type III PKS that of SrsA the of the of in and type III with and that of contained an of the that in of srsB in in of an with a type III PKS that was with a of the of with an in with a of that of contained a found in flavoprotein that a hydroxylase. srsC a of the srsA and srsB in the of srs srsA and and and srsC and a heterologous host, srs genes the the overexpression of the srs and the that in and in the in the the the the the srs genes and the of a of the srs of the the of the srsA srsA and srsB and and srsC and and in contained and with a was of and a of in contained of of in contained and a of in contained and of of the in of the that contained in the in with a a in a of and with the of and and and and an a SrsA was a type III PKS the the the that was a the which the of the of of the and of a this of the and with in the of and that the of and the of and of and that was a of of the the and and the of SrsA and A SrsA the in with the was that the in a aromatic the of polyketide the of in SrsA with a of SrsA SrsA was srsA the the was SrsA in a a of in SrsA a a of the and of in of the the of was and SrsA a and in a and of was the the of was and contained in the SrsA a in a of was SrsA was a of in of SrsA with a and and and and and and and and and SrsA was with and with and of SrsA and was with in a and contained in the SrsA in a of showed that the the aromatic was the polyketide SrsA was a type III PKS that the of a and of srsA in in the of the srs in of the in in the griseus the srsA the of SrsA with a of the of the the the and and in the griseus in srsA was in in the and of the the of the the and of and in the the of in the which that the in the and of of the of the the griseus and with contained of the and of and griseus and with and of of was srsA found that and in the of a type III PKS, which of the of the the of in that the and the of the in griseus and of the and a the in and which showed that the found that was and of of and the griseus of this a the and the showed which in the this of srsA a in the which that the the of was the in srsA the of the that the a aromatic and a and in the and the a of which the the of the and of that the in griseus SrsA a type III PKS that the of of and and a of the of of the of the in the of the SrsA and and of in and that the of the the of the of encoded the in and SrsA encoded the srs in griseus in the that and type III that synthesize and the of type synthases and of the of genes the in the the and in this the the in griseus the and that the of the in griseus in that the of Streptomyces and type and of SrsA of that the in the of the in of the the in of SrsA and of SrsA that of in that SrsA and SrsA a A of SrsA that with an aromatic a that an type III an the SrsA the of of and in the of and the the polyketide that the a the the of A this the of a that of a of and in this in of the of the and the of the the a of a the the of a the the that the A of of a the in type III and and in Streptomyces and in A the of SrsA and that a of that an and of an a the SrsA which of and the type synthases and the of in that the griseus and the an aromatic with a and in the the the and of the the of of the the of griseus in the the a the in the of and in the of the in with the that the in griseus a the srs that showed that the in the and the of the of the in an in which of the of in griseus the the srs of the the in a variety of and bacteria an the of the in the in fungi, and in plants, fungi, and a of a Streptomyces and of a that an in in this Streptomyces a the in griseus the of the srs in which SrsA of and in the of and polyketide the of a type III PKS that and in the of SrsA of and that the with the in an the and of the the Type III PKS, polyketide PKS, polyketide and that the of aromatic in and found that a type III PKS, in the Gram-positive, filamentous bacterium Streptomyces griseus the of a with and the the was the of a type III PKS of bacteria that type III in Streptomyces and of which type III in the of and which the in the the griseus and in and in and found a type III PKS, in type III PKS was SrsA of synthesize in a a of the was an srs of and srsC this the of the srs the in and in of the SrsA was of the of and of in Consistent with this overexpression of srsA in a heterologous host, Streptomyces lividans, the of with and in SrsA and and the of of the was srsA and srsB in lividans, of and srsC of showed that was a and was a the of the operon, a the and griseus in the was and of which that the and in the of the griseus in the of a of the with the that a of genes and in and that the a in the the that in and and and and A griseus was the of was Streptomyces of and srsC in a was with of was a Streptomyces of SrsA in an was and griseus in Streptomyces and with the an the of griseus the the of was of of srsA the of the in an was the of srsA with an and the the and a a the and the of srsB the was the and of in was the and of in of of srsA and srsB the was with and III with a the was the and of in was the and of in of of and srsC the srsC was the in srsC a the of srsB the the of srsC was with with a the and with a the was the and of in was the and of in was the and of in of the of the srsA a of the srsA was with with a the and with a the was the and of in was the and of in was the and of in of a the of srsA was in an and in the the and was with and with a and and the was the and of in was the of in of srsA with the in was with with a the the in the the the and with a the was the and of in was the and of in of was of of and of was the and the was A of the was with and with the was in of with and in a of was and of of and griseus the the that the was the with the was and the was was with and with was a of was with with with and the and the in a of and an was and in with a with and in a of of of a of and of and of a of and of of and of a of and of a of and of a of and of and of a of and of was and with the of and and and in the in and of was of and was the and the was a was and in and was was with and and with and SrsA was of was with a a of the SrsA was SrsA and the of of and in a of of and with of was and the in of of srsA in in the srsA was the with a of A the was with an the and with the the and a the was the and of in A the was with the the and a the and with a the was the and of in the was the and of in was in the of the in was with and griseus in the a of of the was a in which srsA was was a was that in of in the the and the of griseus and in of of was the with of and in of and was of was was the with of and of was the was was the and the was the of the with and with was and the was in of and and and and A griseus was the of was Streptomyces of and srsC in a was with of was a Streptomyces of SrsA in an was and griseus in Streptomyces and with the an the of griseus the the of was of of srsA the of the in an was the of srsA with an and the the and a a the and the of srsB the was the and of in was the and of in of of srsA and srsB the was with and III with a the was the and of in was the and of in of of and srsC the srsC was the in srsC a the of srsB the the of srsC was with with a the and with a the was the and of in was the and of in was the and of in of the of the srsA a of the srsA was with with a the and with a the was the and of in was the and of in was the and of in of a the of srsA was in an and in the the and was with and with a and and the was the and of in was the of in of srsA with the in was with with a the the in the the the and with a the was the and of in was the and of in of was of of and of was the and the was A of the was with and with the was in of with and in a of was and of of and griseus the the that the was the with the was and the was was with and with was a of was with with with and the and the in a of and an was and in with a with and in a of of of a of and of and of a of and of of and of a of and of a of and of a of and of and of a of and of was and with the of and and and in the in and of was of and was the and the was a was and in and was was with and and with and SrsA was of was with a a of the SrsA was SrsA and the of of and in a of of and with of was and the in of of srsA in in the srsA was the with a of A the was with an the and with the the and a the was the and of in A the was with the the and a the and with a the was the and of in the was the and of in was in the of the in was with and griseus in the a of of the was a in which srsA was was a was that in of in the the and the of griseus and in of of was the with of and in of and was of was was the with of and of was the was was the and the was the of the with and with was and the was in of of the srs and of of the srs genes in of srsA the of and the of srsB with the of of the srs genes that an that was a of a a which of srsA a which of that the srs the srs was of in of that a type III PKS and SrsA showed in a type III PKS that of SrsA the of the of in and type III with and that of contained an of the that in of srsB in in of an with a type III PKS that was with a of the of with an in with a of that of contained a found in flavoprotein that a hydroxylase. srsC a of the srsA and srsB in the of srs srsA and and and srsC and a heterologous host, srs genes the the overexpression of the srs and the that in and in the in the the the the the srs genes of the that contained in the in with a a in a of and with the of and and and and an a SrsA was a type III PKS the the the that was a the which the of the of of the and of a this of the and with in the of and that the of and the of and of and that was a of of the the and and the of SrsA and A SrsA the in with the was that the in a aromatic the of polyketide the of in SrsA with a of SrsA SrsA was srsA the the was SrsA in a a of in SrsA a a of the and of in of the the of was and SrsA a and in a and of was the the of was and contained in the SrsA a in a of was SrsA was a of in of SrsA with a and and and and and and and and and SrsA was with and with and of SrsA and was with in a and contained in the SrsA in a of showed that the the aromatic was the polyketide SrsA was a type III PKS that the of a and of srsA in in the of the srs in of the in in the griseus the srsA the of SrsA with a of the of the the the and and in the griseus in srsA was in in the and of the the of the the and of and in the the of in the which that the in the and of of the of the the griseus and with contained of the and of and griseus and with and of of was srsA found that and in the of a type III PKS, which of the of the the of in that the and the of the in griseus and of the and a the in and which showed that the found that was and of of and the griseus of this a the and the showed which in the this of srsA a in the which that the the of was the in srsA the of the that the a aromatic and a and in the and the a of which the the of the and of of the srs and of of the srs genes in of srsA the of and the of srsB with the of of the srs genes that an that was a of a a which of srsA a which of that the srs the srs was of in of that a type III PKS and SrsA showed in a type III PKS that of SrsA the of the of in and type III with and A that of contained an of the that in of srsB in in of an with a type III PKS that was with a of the of with an in with a of that of contained a found in flavoprotein that a hydroxylase. srsC a of the srsA and srsB in the of srs srsA and and and srsC and a heterologous host, srs genes the the overexpression of the srs and the that in and in the in the the the the the srs genes of the that contained in the in with a a in a of and with the of and and and and an a SrsA was a type III PKS the the the that was a the which the of the of of the and of a this of the and with in the of and that the of and the of and of and that was a of SrsA the in with the was that the in a aromatic the of polyketide the of in SrsA with a of SrsA SrsA was srsA the the was SrsA in a a of in SrsA a a of the and of in of the the of was and SrsA a and in a and of was the the of was and contained in the SrsA a in a of was SrsA was a and of SrsA and was with in a and contained in the SrsA in a of showed that the the aromatic was the polyketide SrsA was a type III PKS that the of a and of srsA in in the of the srs in of the in in the griseus the srsA the of SrsA with a of the of the the the and and in the griseus in srsA was in in the and of the the of the the and of and in the the of in the which that the in the and found that and in the of a type III PKS, which of the of the the of in that the and the of the in griseus and of the and a the in and which showed that the found that was and of of and the griseus of this a the and the showed which in the this of srsA a in the which that the the of was the in srsA the of the that the a aromatic and a and in the and the a of which the the of the and of that the in griseus SrsA a type III PKS that the of of and and a of the of of the of the in the of the SrsA and and of in and that the of the the of the of encoded the in and SrsA encoded the srs in griseus in the that and type III that synthesize and the of type synthases and of the of genes the in the the and in this the the in griseus the and that the of the in griseus in that the of Streptomyces and type and of SrsA of that the in the of the in of the the in of SrsA and of SrsA that of in that SrsA and SrsA a A of SrsA that with an aromatic a that an type III an the SrsA the of of and in the of and the the polyketide that the a the the of A this the of a that of a of and in this in of the of the and the of the the a of a the the of a the the that the A of of a the in type III and and in Streptomyces and in A the of SrsA and that a of that an and of an a the SrsA which of and the type synthases and the of in that the griseus and the an aromatic with a and in the the the and of the the of of the the of griseus in the the a the in the of and in the of the in with the that the in griseus a the srs that showed that the in the and the of the of the in an in which of the of in griseus the the srs of the the in a variety of and bacteria an the of the in the in fungi, and in plants, fungi, and a of a Streptomyces and of a that an in in this Streptomyces a the in griseus the of the srs in which SrsA of and in the of and polyketide the of a type III PKS that and in the of SrsA of and that the with the in an the and of the the that the in griseus SrsA a type III PKS that the of of and and a of the of of the of the in the of the SrsA and and of in and that the of the the of the of encoded the in and SrsA encoded the srs in griseus in the that and type III that synthesize and the of type synthases and of the of genes the in the the and in this the the in griseus the and that the of the in griseus in that the of Streptomyces and type and of SrsA of that the in the of the in of the the in of SrsA and of SrsA that of in that SrsA and SrsA a A of SrsA that with an aromatic a that an type III an the SrsA the of of and in the of and the the polyketide that the a the the of A this the of a that of a of and in this in of the of the and the of the the a of a the the of a the the that the A of of a the SrsA in type III and and in Streptomyces and in A the of SrsA and that a of that an and of an a the SrsA which of and the type synthases and the of in that the griseus and the an aromatic with a and in the the the and of the the of of the the of griseus in the the a the in the of and in the of the in Consistent with the that the in griseus a the srs that showed that the in the and the of the of the in an in which of the of in griseus the the srs of the the in a variety of and bacteria an the of the in the in fungi, and in plants, fungi, and a of a Streptomyces and of a that an in in this Streptomyces a the in griseus the of the srs in which SrsA of and in the of and polyketide the of a type III PKS that and in the of SrsA of and that the with the in an the and of the the of with with