Gene cluster for biosynthesis of cornexistin and hydroxycornexistinThe invention pertains to the field of production of natural products and, in particular, in the field of production of cornexistin and hydroxycornexistin. It provides polynucleotides encoding polypeptides involved in the biosynthesis of cornexistin and hydroxycornexistin as well as vectors and recombinant microorganisms comprising such polynucleotides. Also provided are methods for the production of natural products, in particular methods for the production of cornexistin and hydroxycornexistin, using such polynucleotides and polpeptides encoded therein, as well as vectors and recombinant microorganisms comprising such polynucleotides and polypeptides.A recombinant microorganism, comprisesa) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:13 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andb) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:15 or 89 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, preferably have with seq id no:89 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andc) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:17 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andd) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:19 and/or 105 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, preferably have with seqid no:105 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, ande) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:21 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andf) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:23 and/or 121 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, preferably have with seqid no:121 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andg) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:25 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andh) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:27 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andi) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:29 and/or 141 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, preferably have with seqid no:29 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andj) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:31 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andk) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:33 and/or 158 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, preferably have with seqid no:158 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andl) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:35 and/or 169 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, preferably have with seqid no:169 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andm) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:37 and/or 180 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andn) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:39 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, ando) at least one expression cassette of following polypeptide, described polypeptide have with seq id no:41 and/or 196 at least 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% same aminoacid sequence, andwherein a) at least one expression cassette o) be recombinant expression cassettes.
코르넥시스틴 및 히드록시코르넥시스틴의 생합성을 위한 유전자 클러스터본 발명은 천연 산물의 생성 분야, 특히 코르넥시스틴 및 히드록시코르넥시스틴의 생성 분야에 관한 것이다. 본 발명은 코르넥시스틴 및 히드록시코르넥시스틴의 생합성에 관여한 폴리펩티드를 코딩하는 폴리뉴클레오티드 뿐만 아니라 이러한 폴리뉴클레오티드를 포함하는 벡터 및 재조합 미생물을 제공한다. 또한, 상기 폴리뉴클레오티드 및 그 안에 코딩된 폴리펩티드 뿐만 아니라 상기 폴리뉴클레오티드 및 폴리펩티드를 포함하는 벡터 및 재조합 미생물을 이용하여, 천연 산물을 생성하는 방법, 특히 코르넥시스틴 및 히드록시코르넥시스틴을 생성하는 방법을 제공한다.a) 서열 13과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및b) 서열 15 또는 89와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖고, 바람직하게 서열 89와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및c) 서열 17과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및d) 서열 19 및/또는 105와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖고, 바람직하게 서열 105와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및e) 서열 21과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및f) 서열 23 및/또는 121과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖고, 바람직하게 서열 121과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및g) 서열 25와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및h) 서열 27과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및i) 서열 29 및/또는 141과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖고, 바람직하게 서열 29와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및j) 서열 31과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및k) 서열 33 및/또는 158과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖고, 바람직하게 서열 158과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및l) 서열 35 및/또는 169와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖고, 바람직하게 서열 169와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및m) 서열 37 및/또는 180과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및n) 서열 39와 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트, 및o) 서열 41 및/또는 196과 적어도 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 갖는 폴리펩티드에 대한 하나 이상의 발현 카세트를 포함하며, 여기서 a) 내지 o)의 발현 카세트 중 하나 이상은 재조합 발현 카세트인 재조합 미생물.