When anenoyl reductase enzyme of a modular polyketide synthase reduces a propionate extender unit that has been newly added to the growing polyketide chain, the resulting methyl branch may have either S or R configuration. We have uncovered a correlation between the presence or absence of a unique tyrosine residue in the ER active site and the chirality of the methyl branch that is introduced. When this position in the active site is occupied by a tyrosine residue, the methyl branch has S configuration, otherwise it has R configuration. In a model PKS in vivo, a mutation (Tyr to Val) in an erythromycin PKS-derived ER caused a switch in the methyl branch configurationin the product from S to R. In contrast, alteration (Val to Tyr) at this position in a rapamycin-derived PKS ER was insufficient to achieve a switch from R to S, showing that additional residues also participate in stereo control of enoylreduction.

The biosynthetic gene cluster for tetronomycin (TMN), a polyether ionophoric antibiotic that contains four different types of ring, including the distinctive tetronic acid moiety, has been cloned from Streptomyces sp. NRRL11266. The sequenced tmn locus (113234 bp) contains six modular polyketide synthase (PKS) genes and a further 27 open-reading frames. Based on sequence comparison to related biosynthetic gene clusters, the majority of these can be assigned a plausible role in TMN biosynthesis. The identity of the cluster, and the requirement for a number of individual genes, especially those hypothesised to contribute aglycerate unit to the formation of the tetronate ring, were confirmed by specific gene disruption. However, two large genes that are predicted to encode together a multifunctional PKS of a highly unusual type seem not to be involved in this pathway since deletion of one of them did not alter tetronomycin production. Unlike previously characterised polyether PKS systems, oxidative cyclisation appears to take place on the modular PKS rather than after transfer to a separate carrier protein, while tetronate ring formation and concomitant chain release share common mechanistic features with spirotetronate biosynthesis.

The biosynthetic pathway to the unusual tetronate ring of certain polyketide natural products, including the antibiotics abyssomicin and tetronomycin (TMN) and the antitumour compound chlorothricin (CHL), is presently unknown. The gene clusters governing chlorothricin and tetronomycin biosynthesis both contain a gene encoding an atypical member of the FkbH family of enzymes, which has previously been shown to synthesise glyceryl-S-acylcarrier protein (ACP) as the first step in production of unusual extender units for modular polyketide biosynthesis. We show here that purified recombinant FkbH-like protein, Tmn16, from the TMN gene cluster catalyses the efficient transfer of a glyceryl moiety from D-1,3-bisphosphoglycerate (1,3-BPG) to either of the dedicated ACPs, Tmn7a and ChlD2, to form glyceryl-S-ACP, which directly implicates this compound as an intermediate in tetronate biosynthesis as well. Neither Tmn16 nor Tmn7a produced glyceryl-S-ACP when incubated, respectively, with analogous ACP and FkbH-like proteins from a known extender-unit pathway; this indicates a highly selective channelling of glycolytic metabolites into tetronate biosynthesis.

实验采用庆大霉素对链霉菌702原生质体致死突变标志的紫外诱变筛选模型，以提高其所产抗真菌生物活性物质的产量。实验结果表明,紫外线处理40s 时，致死率达67.15%，突变率高达20.18%，突变株经过摇瓶筛选获得高产菌株42-23-111，产素单位达到949 μg/mL，比出发菌株提高了23.2%。

In order to increase the yield of antifungi substance, UV induced-mutation and the protoplasts resistance-gentamycin mutational labelling selection model was used to screen high-yield mutants of Streptomyces 702. The results showed that the gentamycin-resistant mutational frequency of the protoplasts of Streptomyces 702 treated by UV with 40 seconds was up to 20.18% and the lethal rate was 67.15%. High antifungi substance-producing mutant 42-23-111 was isolated in the screening experiments, and its yield of antifungi substance reached 949 μg/mL, which was 23.2% higher than that produced by its parent strain.

采用庆大霉素对链霉菌702原生质体致死突变标志的NTG诱变筛选模型，以提高其所产抗真菌生物活性物质的产量。实验结果表明，NTG处理90 min时，致死率达71.32%,突变率高达48.58%，突变株经过摇瓶筛选获得高产菌株NTG-20，其所产抗真菌活性物质的生物效价达到1680 μg/mL，比出发菌株产量提高了118%，菌株NTG-12和NTG-3的产量也比出发菌株产量相应提高了95%和70%。

In the paper, NTG mutation screening of resistance-chemical mutational label of protoplasts from Streptomyces 702 was adopted to increase the yield of antifungi substance. The results showed that the lethality and mutation rate was 71.32% and 48.58%, respectively, and high antifungi substance-producing mutant NTG-20 was isolated by shaking flask culture, biological potency of antifungal bioactive substance reached 1680 g/mL, which improved 118% than its parent stain, the yield from NTG-12 and NTG-3 improved 95% and 70% than the parent strain.